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Cellular function and molecular structure of ecto-nucleotidases

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Abstract

Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ecto-nucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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Abbreviations

ACR:

Apyrase-conserved regions

AMPCP:

α,β-Methylene-ADP

AMPPNP:

β,γ-Imidoadenosine 5′-triphosphate

AP:

Alkaline phosphatases

ATX:

Autotaxin

CAN:

Calcium-activated nucleotidase

CHO:

Chinese hamster ovary

ECD:

Extracellular domain

eN:

5′-Nucleotidase

ER:

Endoplasmic reticulum

FRET:

Fluorescence resonance energy transfer

GCAP:

Germ cell AP

GPC:

Glycerophosphorylcholine

GPI:

Glycosylphosphatidylinositol

IAP:

Intestinal AP

LPA:

Lysophosphatidic acid

LPC:

Lysophosphatidylcholine

LPS:

Lipopolysaccharide

MALDI:

Matrix-assisted laser desorption/ionization

MDCK:

Madin–Darby canine kidney

MS:

Mass spectrometry

NDP:

Nucleoside diphosphate

NLD:

Nuclease-like domain

NMP:

Nucleoside monophosphate

NMN:

Nicotinamide mononucleotide

NMR:

Nuclear magnetic resonance

NPP:

Nucleotide pyrophosphatase/phosphodiesterase

NR:

Nicotinamide riboside

NTP:

Nucleoside triphosphate

NTPDase:

Nucleoside triphosphate diphosphohydrolase

PAP:

Prostatic acid phosphatase

PDB:

Protein Data Bank

PDE:

Phosphodiesterase

PI-PLC:

Phosphatidylinositol-specific phospholipase C

PLAP:

Placental AP

PLP:

Pyridoxal 5′-phosphate

PMA:

Phorbol myristate acetate

pNPPC:

p-Nitrophenyl phosphorylcholine

PPi :

Pyrophosphate

S1P:

Sphingosine-1-phosphate

SMB:

Somatomedin B

SPC:

Sphingosylphosphorylcholine

RanBPM:

Ran Binding Protein M

TMD:

Transmembrane domain

TNAP:

Tissue nonspecific AP

TRAP:

Tartrate-resistant acid phosphatase

References

  1. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797

    Article  PubMed  CAS  Google Scholar 

  2. Zimmermann H, Mishra SK, Shukla V, Langer D, Gampe K, Grimm I, Delic J, Braun N (2007) Ecto-nucleotidases, molecular properties and functional impact. An R Acad Nac Farm 73:537–566

    CAS  Google Scholar 

  3. Zimmermann H (2008) ATP and acetylcholine, equal brethren. Neurochem Int 52:634–648

    Article  PubMed  CAS  Google Scholar 

  4. Burnstock G (2006) Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev 58:58–86

    Article  PubMed  CAS  Google Scholar 

  5. King AE, Ackley MA, Cass CE, Young JD, Baldwin SA (2006) Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharm Sci 27:416–425

    Article  PubMed  CAS  Google Scholar 

  6. Johnson K, Polewski M, Van Etten D, Terkeltaub R (2005) Chondrogenesis mediated by PPi depletion promotes spontaneous aortic calcification in NPP1−/− mice. Arterioscler Thromb Vasc Biol 25:686–691

    Article  PubMed  CAS  Google Scholar 

  7. Villa-Bellosta R, Wang XN, Millán JL, Dubyak GR, ONeill WC (2011) Extracellular pyrophosphate metabolism and calcification in vascular smooth muscle. Amer J Physiol Heart Circ Phy 301:H61–H68

    Article  CAS  Google Scholar 

  8. Ciana P, Fumagalli M, Trincavelli ML, Verderio C, Rosa P, Lecca D, Ferrario S, Parravicini C, Capra V, Gelosa P, Guerrini U, Belcredito S, Cimino M, Sironi L, Tremoli E, Rovati GE, Martini C, Abbracchio MP (2006) The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J 25:4615–4627

    Article  PubMed  CAS  Google Scholar 

  9. Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA (2006) International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58:281–341

    Article  PubMed  CAS  Google Scholar 

  10. Harden TK, Sesma JI, Fricks IP, Lazarowski ER (2010) Signalling and pharmacological properties of the P2Y14 receptor. Acta Physiol 199:149–160

    Article  CAS  Google Scholar 

  11. Mutafova-Yambolieva VN, Hwang SJ, Hao X, Chen H, Zhu MX, Wood JD, Ward SM, Sanders KM (2007) β-Nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Proc Natl Acad Sci USA 104:16359–16364

    Article  PubMed  CAS  Google Scholar 

  12. Hwang SJ, Durnin L, Dwyer L, Rhee PL, Ward SM, Koh SD, Sanders KM, Mutafova-Yambolieva VN (2011) β-Nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons. Gastroenterology 140:608–U347

    Article  PubMed  CAS  Google Scholar 

  13. Gallego D, Gil V, Aleu J, Martinez-Cutillas M, Clave P, Jimenez M (2011) Pharmacological characterization of purinergic inhibitory neuromuscular transmission in the human colon. Neurogastroenterol Motil 23:792–e338

    Article  PubMed  CAS  Google Scholar 

  14. Gustafsson AJ, Muraro L, Dahlberg C, Migaud M, Chevallier O, Khanh HN, Krishnan K, Li NL, Islam MS (2011) ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor. Mol Cell Endocrinol 337:122–123

    Article  CAS  Google Scholar 

  15. Ehrlich YH, Hogan MV, Pawlowska Z, Wieraszko A, Katz E, Sobocki T, Babinska A, Kornecki E (1998) Surface protein phosphorylation by ecto-protein kinases. Role in neuronal development and synaptic plasticity. Adv Exp Med Biol 446:51–71

    Article  PubMed  CAS  Google Scholar 

  16. Rodriguez FA, Contreras C, Bolanos-Garcia V, Allende JE (2008) Protein kinase CK2 as an ectokinase: the role of the regulatory CK2beta subunit. Proc Natl Acad Sci USA 105:5693–5698

    Article  PubMed  CAS  Google Scholar 

  17. Seman M, Adriouch S, Scheuplein F, Krebs C, Freese D, Glowacki G, Deterre P, Haag F, Koch-Nolte F (2003) NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19:571–582

    Article  PubMed  CAS  Google Scholar 

  18. Quintero IB, Araujo CL, Pulkka AE, Wirkkala RS, Herrala AM, Eskelinen EL, Jokitalo E, Hellström PA, Tuominen HJ, Hirvikoski PP, Vihko PT (2007) Prostatic acid phosphatase is not a prostate specific target. Cancer Res 67:6549–6554

    Article  PubMed  CAS  Google Scholar 

  19. Zylka MJ, Sowa NA, Taylor-Blake B, Twomey MA, Herrala A, Voikar V, Vihko P (2008) Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine. Neuron 60:111–122

    Article  PubMed  CAS  Google Scholar 

  20. Sowa NA, Vadakkan KI, Zylka MJ (2009) Recombinant mouse PAP has pH-dependent ectonucleotidase activity and acts through A1-adenosine receptors to mediate antinociception. PLoS One 4:e4248

    Article  PubMed  CAS  Google Scholar 

  21. Zylka MJ (2011) Pain-relieving prospects for adenosine receptors and ectonucleotidases. Trends Mol Med 17:188–196

    Article  PubMed  CAS  Google Scholar 

  22. Mitic N, Valizadeh M, Leung EW, de JJ, Hamilton S, Hume DA, Cassady AI, Schenk G (2005) Human tartrate-resistant acid phosphatase becomes an effective ATPase upon proteolytic activation. Arch Biochem Biophys 439:154–164

    Article  PubMed  CAS  Google Scholar 

  23. Oddie GW, Schenk G, Angel NZ, Walsh N, Guddat LW, de Jersey J, Cassady AI, Hamilton SE, Hume DA (2000) Structure, function, and regulation of tartrate-resistant acid phosphatase. Bone 27:575–584

    Article  PubMed  CAS  Google Scholar 

  24. Kaunitz JD, Yamaguchi DT (2008) TNAP, TrAP, ecto-purinergic signaling, and bone remodeling. J Cell Biochem 105:655–662

    Article  PubMed  CAS  Google Scholar 

  25. Smith TM, Kirley TL (2006) The calcium activated nucleotidases: a diverse family of soluble and membrane associated nucleotide hydrolyzing enzymes. Purinergic Signal 2:327–333

    Article  PubMed  CAS  Google Scholar 

  26. Sandona D, Gastaldello S, Martinello T, Betto R (2004) Characterization of the ATP-hydrolysing activity of alpha-sarcoglycan. Biochem J 381:105–112

    Article  PubMed  CAS  Google Scholar 

  27. Dzhandzhugazyan K, Bock E (1993) Demonstration of (Ca2+-Mg2+)-ATPase activity of the neural cell adhesion molecule. FEBS Lett 336:279–283

    Article  PubMed  CAS  Google Scholar 

  28. Champagne E, Martinez LO, Collet X, Barbaras R (2006) Ecto-F1F0 ATP synthase/F1 ATPase: metabolic and immunological functions. Curr Opin Lipidol 17:279–284

    Article  PubMed  CAS  Google Scholar 

  29. Fu Y, Hou YJ, Fu CL, Gu MX, Li CH, Kong W, Wang XA, Shyy JYJ, Zhu Y (2011) A novel mechanism of γ/δ T-lymphocyte and endothelial activation by shear stress the role of ecto-ATP synthase β chain. Circ Res 108:410–417

    Article  PubMed  CAS  Google Scholar 

  30. Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. BBA Mol Cell Res 1783:673–694

    CAS  Google Scholar 

  31. Deaglio S, Malavasi F (2006) The CD38/CD157 mammalian gene family: an evolutionary paradigm for other leucocyte surface enzymes. Purinergic Signal 2:431–441

    Article  PubMed  CAS  Google Scholar 

  32. Kukulski F, Levesque SA, Sévigny J (2011) Impact of ectoenzymes on P2 and P1 receptor signaling. Adv Pharmacol 61:263–299

    Article  PubMed  CAS  Google Scholar 

  33. Yegutkin GG, Henttinen T, Jalkanen S (2001) Extracellular ATP formation on vascular endothelial cells is mediated by ecto-nucleotide kinase activities via phosphotransfer reactions. FASEB J 15:251–260

    Article  PubMed  CAS  Google Scholar 

  34. Yegutkin GG, Mikhailov A, Samburski SS, Jalkanen S (2006) The detection of micromolar pericellular ATP pool on lymphocyte surface by using lymphoid ecto-adenylate kinase as intrinsic ATP sensor. Mol Biol Cell 17:3378–3385

    Article  PubMed  CAS  Google Scholar 

  35. Zimmermann H (2001) Ecto-nucleotidases. In: Abbracchio MP, Williams M (eds) Handbook of experimental pharmacology. Purinergic and pyrimidergic signalling, vol 151/I. Springer, Heidelberg, pp 209–250

    Google Scholar 

  36. Robson SC, Sévigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal 2:409–430

    Article  PubMed  CAS  Google Scholar 

  37. Knowles AF (2011) The GDA1_CD39 superfamily: NTPDases with diverse functions. Purinergic Signal 7:21–45

    Article  PubMed  CAS  Google Scholar 

  38. Zimmermann H, Beaudoin AR, Bollen M, Goding JW, Guidotti G, Kirley TL, Robson SC, Sano K (2000) Proposed nomenclature for two novel nucleotide hydrolyzing enzyme families expressed on the cell surface. In: Lemmens R, vanDuffel L (eds) Ecto-ATPases and related ectonucleotidases. Shaker, Maastricht, pp 1–8

    Google Scholar 

  39. Zimmermann H (2001) Ectonucleotidases: some recent developments and a note on nomenclature. Drug Dev Res 52:44–56

    Article  CAS  Google Scholar 

  40. Lavoie ÉG, Gulbransen BD, Martín-Satué M, Aliagas E, Sharkey KA, Sévigny J (2011) Ectonucleotidases in the digestive system: focus on NTPDase3 localization. Amer J Physiol Gastrointest L 300:G608–G620

    Article  CAS  Google Scholar 

  41. Enjyoji K, Sévigny J, Lin Y, Frenette P, Christie PD, Schulte am Esch J, Imai M, Edelberger JM, Rayburn H, Lech M, Beeler DM, Csizmadia E, Wagner DD, Robson SC, Rosenberg RD (1999) Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nature Med 5:1010–1017

    Article  PubMed  CAS  Google Scholar 

  42. Pinsky DJ, Broekman MJ, Peschon JJ, Stocking KL, Fujita T, Ramasamy R, Connolly ES, Huang J, Kiss S, Zhang Y, Choudhri TF, McTaggart RA, Liao H, Drospoulos JHF, Price VL, Marcus AJ, Maliszewski CR (2002) Elucidation of the thromboregulatory role of CD39/ectoapyrase in the ischemic brain. J Clin Invest 109:1031–1040

    PubMed  CAS  Google Scholar 

  43. Mizumoto N, Kumamoto T, Robson SC, Sévigny J, Matsue H, Enjyoji K, Takashima A (2002) CD39 is the dominant Langerhans cell associated ecto-NTPDase: modulatory roles in inflammation and immune responsiveness. Nature Med 8:358–365

    Article  PubMed  CAS  Google Scholar 

  44. Dwyer KM, Deaglio S, Gao W, Friedman D, Strom TB, Robson SC (2007) CD39 and control of cellular immune responses. Purinergic Signal 3:171–180

    Article  PubMed  CAS  Google Scholar 

  45. Deaglio S, Robson SC (2011) Ectonucleotidases as regulators of purinergic signaling in thrombosis, inflammation, and immunity. Adv Pharmacol 61:301–332

    Article  PubMed  CAS  Google Scholar 

  46. Sévigny J, Sundberg C, Braun N, Guckelberger O, Csizmadia E, Qawi I, Imai M, Zimmermann H, Robson SC (2002) Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation. Blood 99:2801–2809

    Article  PubMed  Google Scholar 

  47. Robson SC, Wu Y, Sun XF, Knosalla C, Dwyer K, Enjyoji K (2005) Ectonucleotidases of CD39 family modulate vascular inflammation and thrombosis in transplantation. Semin Thromb Hemostasis 31:217–233

    Article  CAS  Google Scholar 

  48. Marcus AJ, Broekman MJ, Drosopoulos JHF, Olson KE, Islam N, Pinsky DJ, Levi R (2005) Role of CD39 (NTPDase-1) in thromboregulation, cerebroprotection, and cardioprotection. Semin Thromb Hemostasis 31:234–246

    Article  CAS  Google Scholar 

  49. Kauffenstein G, Fürstenau CR, D'Orleans-Juste P, Sévigny J (2010) The ecto-nucleotidase NTPDase1 differentially regulates P2Y1 and P2Y2 receptor-dependent vasorelaxation. Brit J Pharmacol 159:576–585

    Article  CAS  Google Scholar 

  50. Kauffenstein G, Drouin A, Thorin-Trescases N, Bachelard H, Robaye B, D'Orleans-Juste P, Marceau F, Thorin E, Sévigny J (2010) NTPDase1 (CD39) controls nucleotide-dependent vasoconstriction in mouse. Cardiovasc Res 85:204–213

    Article  PubMed  CAS  Google Scholar 

  51. Bartel DL, Sullivan SL, Lavoie ÉG, Sévigny J, Finger TE (2006) Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J Comp Neurol 497:1–12

    Article  PubMed  CAS  Google Scholar 

  52. Braun N, Sévigny J, Mishra S, Robson SC, Barth SW, Gerstberger R, Hammer K, Zimmermann H (2003) Expression of the ecto-ATPase NTPDase2 in the germinal zones of the developing and adult rat brain. Eur J Neurosci 17:1355–1364

    Article  PubMed  Google Scholar 

  53. Braun N, Sévigny J, Robson SC, Hammer K, Hanani M, Zimmermann H (2004) Association of the ecto-ATPase NTPDase2 with glial cells of the peripheral nervous system. Glia 45:124–132

    Article  PubMed  Google Scholar 

  54. Shukla V, Zimmermann H, Wang L, Kettenmann H, Raab S, Hammer K, Sévigny J, Robson SC, Braun N (2005) Functional expression of the ecto-ATPase NTPDase2 and of nucleotide receptors by neuronal progenitor cells in the adult murine hippocampus. J Neurosci Res 80:600–610

    Article  PubMed  CAS  Google Scholar 

  55. Mishra SK, Braun N, Shukla V, Füllgrabe M, Schomerus C, Korf H-W, Gachet C, Ikehara Y, Sévigny J, Robson SC, Zimmermann H (2006) Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation. Development 133:675–684

    Article  PubMed  CAS  Google Scholar 

  56. Vongtau HO, Lavoie ÉG, Sévigny J, Molliver DC (2011) Distribution of ecto-nucleotidases in mouse sensory circuits suggests roles for nucleoside triphosphate diphosphohydrolyse-3 in nociception and mechanoreception. Neuroscience 193:387–398

    Article  PubMed  CAS  Google Scholar 

  57. Zimmermann H (2011) Purinergic signaling in neural development. Semin Cell Dev Biol 22:194–204

    Article  PubMed  CAS  Google Scholar 

  58. Massé K, Bhamra S, Eason R, Dale N, Jones EA (2007) Purine-mediated signalling triggers eye development. Nature 449:1058–1062

    Article  PubMed  CAS  Google Scholar 

  59. Belcher SM, Zsarnovzky A, Crawford PA, Hemani H, Spurling L, Kirley TL (2006) Immunolocalization of ecto-nucleoside triphosphate diphosphohydrolase 3 in rat brain: implications for modulation of multiple homeostatic systems including feeding and sleep wake behaviors. Neuroscience 137:1331–1346

    Article  PubMed  CAS  Google Scholar 

  60. Lavoie ÉG, Fausther M, Kauffenstein G, Kukulski F, Kunzli BM, Friess H, Sévigny J (2010) Identification of the ectonucleotidases expressed in mouse, rat, and human Langerhans islets: potential role of NTPDase3 in insulin secretion. Amer J Physiol Endocrinol Met 299:F647–F656

    Article  CAS  Google Scholar 

  61. Burch LH, Picher M (2006) E-NTPDases in human airways: regulation and relevance for chronic lung diseases. Purinergic Signalling 2:399–408

    Article  PubMed  CAS  Google Scholar 

  62. Fausther M, Pelletier J, Ribeiro CM, Sévigny J, Picher M (2010) Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3. Amer J Physiol Lung Cell M Ph 298:L804–L818

    Article  CAS  Google Scholar 

  63. Biederbick A, Kosan C, Kunz J, Elsässer HP (2000) First apyrase splice variants have different enzymatic properties. J Biol Chem 275:19018–19024

    Article  PubMed  CAS  Google Scholar 

  64. Shi JD, Kukar T, Wang CY, Li QZ, Cruz PE, Davoodi-Semiromi A, Yang P, Gu YR, Lian W, Wu DH, She JX (2001) Molecular cloning and characterization of a novel mammalian endo-apyrase (LALP1). J Biol Chem 276:17474–17478

    Article  PubMed  CAS  Google Scholar 

  65. Yeung G, Mulero JJ, McGowan DW, Bajwa SS, Ford JE (2000) CD39L2, a gene encoding a human nucleoside diphosphatase, predominantly expressed in the heart. Biochemistry USA 39:12916–12923

    Article  CAS  Google Scholar 

  66. O'Keeffe MG, Thorne PR, Housley GD, Robson SC, Vlajkovic SM (2010) Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat cochlea. Histochemistry Cell Biol 133:425–436

    Article  CAS  Google Scholar 

  67. Paéz JG, Recio JA, Rouzaut A, Notario V (2001) Identity between the PCPH proto-oncogene and the CD39L4 (ENTPD5) ectonucleoside triphosphate diphosphohydrolase gene. Int J Oncol 19:1249–1254

    PubMed  Google Scholar 

  68. Fang M, Shen Z, Huang S, Zhao L, Chen S, Mak TW, Wang X (2010) The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 143:711–724

    Article  PubMed  CAS  Google Scholar 

  69. Kukulski F, Lévesque SA, Lavoie ÉG, Lecka J, Bigonnesse F, Knowles AF, Robson SC, Kirley TL, Sévigny J (2005) Comparative hydrolysis of P2 receptor agonists by NTPDase 1, 2, 3 and 8. Purinergic Signal 1:193–204

    Article  PubMed  CAS  Google Scholar 

  70. Heine P, Braun N, Zimmermann H (1999) Functional characterization of rat ecto-ATPase and ecto-ATP diphosphohydrolase after heterologous expression in CHO cells. Eur J Biochem 262:102–107

    Article  PubMed  CAS  Google Scholar 

  71. Knowles AF, Li C (2006) Molecular cloning and characterization of expressed human ecto-nucleoside triphosphate diphosphohydrolase 8 (E-NTPDase 8) and its soluble extracellular domain. Biochemistry USA 45:7323–7333

    Article  CAS  Google Scholar 

  72. Fausther M, Lecka J, Kukulski F, Levesque SA, Pelletier J, Zimmermann H, Dranoff JA, Sévigny J (2007) Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8. Amer J Physiol Gastrointest L 292:G785–G795

    Article  CAS  Google Scholar 

  73. Musi E, Islam N, Drosopoulos JHF (2007) Constraints imposed by transmembrane domains affect enzymatic activity of membrane-associated human CD39/NTPDase1 mutants. Arch Biochem Biophys 461:30–39

    Article  PubMed  CAS  Google Scholar 

  74. Chen W, Guidotti G (2001) Soluble apyrases release ADP during ATP hydrolysis. Biochem Biophys Res Commun 282:90–95

    Article  PubMed  CAS  Google Scholar 

  75. Chiang WC, Knowles AF (2008) Transmembrane domain interactions affect the stability of the extracellular domain of the human NTPDase 2. Arch Biochem Biophys 472:89–99

    Article  PubMed  CAS  Google Scholar 

  76. Wang TF, Guidotti G (1998) Golgi localization and functional expression of human uridine diphosphatase. J Biol Chem 273:11392–11399

    Article  PubMed  CAS  Google Scholar 

  77. Trombetta ES, Helenius A (1999) Glycoprotein reglycosylation and nucleotide sugar utilization in the secretory pathway: identification of a nucleoside diphosphatase in the endoplasmic reticulum. EMBO J 18:3282–3292

    Article  PubMed  CAS  Google Scholar 

  78. Braun N, Fengler S, Ebeling C, Servos J, Zimmermann H (2000) Sequencing, functional expression and characterization of NTPDase6, a nucleoside diphosphatase and novel member of the ecto-nucleoside triphosphate diphosphohydrolase family. Biochem J 351:639–647

    Article  PubMed  CAS  Google Scholar 

  79. Ivanenkov VV, Murphy-Piedmonte DM, Kirley TL (2003) Bacterial expression, characterization, and disulfide bond determination of soluble human NTPDase6 (CD39L2) nucleotidase: implications for structure and function. Biochemistry USA 42:11726–11735

    Article  CAS  Google Scholar 

  80. Zhong XT, Malhotra R, Woodruff R, Guidotti G (2001) Mammalian plasma membrane ecto-nucleoside triphosphate diphosphohydrolase 1, CD39, is not active intracellularly—the N-glycosylation state of CD39 correlates with surface activity and localization. J Biol Chem 276:41518–41525

    Article  PubMed  CAS  Google Scholar 

  81. Ivanenkov VV, Sévigny J, Kirley TL (2008) Trafficking and intracellular ATPase activity of human ecto-nucleotidase NTPDase3 and the effect of ER-targeted NTPDase3 on protein folding. Biochemistry USA 47:9184–9197

    Article  CAS  Google Scholar 

  82. Handa M, Guidotti G (1996) Purification and cloning of a soluble ATP-diphosphohydrolase (apyrase) from potato tubers (Solanum tuberosum). Biochem Biophys Res Commun 218:916–923

    Article  PubMed  CAS  Google Scholar 

  83. Schulte am Esch J, Sévigny J, Kaczmarek E, Siegel JB, Imai M, Koziak K, Beaudoin AR, Robson SC (1999) Structural elements and limited proteolysis of CD39 influence ATP diphosphohydrolase activity. Biochemistry USA 38:2248–2258

    Article  CAS  Google Scholar 

  84. Smith TM, Kirley TL (1999) Site-directed mutagenesis of a human brain ecto-apyrase: evidence that the E-type ATPases are related to the actin/heat shock 70/sugar kinase superfamily. Biochemistry USA 38:321–328

    Article  CAS  Google Scholar 

  85. Maliszewski CR, DeLepesse GJT, Schoenborn MA, Armitage RJ, Fanslow WC, Nakajima T, Baker E, Sutherland GR, Poindexter K, Birks C, Alpert A, Friend D, Gimpel SD, Gayle RB (1994) The CD39 lymphoid cell activation antigen: molecular cloning and structural characterization. J Immunol 153:3574–3583

    PubMed  CAS  Google Scholar 

  86. Kansas GS, Wood GS, Tedder TF (1991) Expression, distribution, and biochemistry of human CD39: role in activation-associated homotypic adhesion of lymphocytes. J Immunol 146:2235–2244

    PubMed  CAS  Google Scholar 

  87. Christoforidis S, Papamarcaki T, Galaris D, Kellner R, Tsolas O (1995) Purification and properties of human placental ATP diphosphohydrolase. Eur J Biochem 234:66–74

    Article  PubMed  CAS  Google Scholar 

  88. Wang TF, Guidotti G (1996) CD39 is an ecto-(Ca2+, Mg2+)-apyrase. J Biol Chem 271:9898–9901

    Article  PubMed  CAS  Google Scholar 

  89. Kaczmarek E, Siegel JB, Sévigny J, Koziak K, Hancock WW, Beaudoin A, Bach FH, Robson SC (1997) Vascular ATP diphosphohydrolase (CD39/ATPDase). In: Plesner L, Kirley TL, Knowles AF (eds) Ecto-ATPases. Recent progress on structure and function. Plenum, New York, pp 171–185

    Google Scholar 

  90. Makita K, Shimoyama T, Sakurai Y, Yagi H, Matsumoto M, Narita N, Sakamoto Y, Saito S, Ikeda Y, Suzuki M, Titani K, Fujimura Y (1998) Placental ecto-ATP diphosphohydrolase: its structural feature distinct from CD39, localization and inhibition on shear-induced platelet aggregation. Int J Hematol 68:297–310

    Article  PubMed  CAS  Google Scholar 

  91. Matsumoto M, Sakurai Y, Kokubo T, Yagi H, Makita K, Matsui T, Titani K, Fujimura Y, Narita N (1999) The cDNA cloning of human placental ecto-ATP diphosphohydrolases I and II. FEBS Lett 453:335–340

    Article  PubMed  CAS  Google Scholar 

  92. Kittel A, Kaczmarek E, Sévigny J, Lengyel K, Csizmadia E, Robson SC (1999) CD39 as a caveolar-associated ectonucleotidase. Biochem Biophys Res Commun 262:596–599

    Article  PubMed  CAS  Google Scholar 

  93. Koziak K, Kaczmarek E, Kittel A, Sévigny J, Blusztajn JK, Schulte am Esch J, Imai M, Guckelberger O, Goepfert C, Qawi I, Robson SC (2000) Palmitoylation targets CD39/endothelial ATP diphosphohydrolase to caveolae. J Biol Chem 275:2057–2062

    Article  PubMed  CAS  Google Scholar 

  94. Kittel A, Csapo Z, Csizmadia E, Jackson SW, Robson SC (2004) Co-localization of P2Y1 receptor and NTPDase1/CD39 within caveolae in human placenta. Eur J Histochem 48:253–259

    PubMed  CAS  Google Scholar 

  95. Papanikolaou A, Papafotika A, Murphy C, Papamarcaki T, Tsolas O, Drab M, Kurzchalia TV, Kasper M, Christoforidis S (2005) Cholesterol-dependent lipid assemblies regulate the activity of the ecto-nucleotidase CD39. J Biol Chem 280:26406–26414

    Article  PubMed  CAS  Google Scholar 

  96. Knowles AF, Chiang WC (2003) Enzymatic and transcriptional regulation of human ecto-ATPase/E-NTPDase2. Arch Biochem Biophys 418:217–227

    Article  PubMed  CAS  Google Scholar 

  97. Kegel B, Braun N, Heine P, Maliszewski CR, Zimmermann H (1997) An ecto-ATPase and an ecto-ATP diphosphohydrolase are expressed in rat brain. Neuropharmacology 36:1189–1200

    Article  PubMed  CAS  Google Scholar 

  98. Mateo J, Harden TK, Boyer JL (1999) Functional expression of a cDNA encoding a human ecto-ATPase. Brit J Pharmacol 128:396–402

    Article  CAS  Google Scholar 

  99. Mateo J, Kreda S, Henry CE, Harden TK, Boyer JL (2003) Requirement of Cys(399) for processing of the human ecto-ATPase (NTPDase2) and its implications for determination of the activities of splice variants of the enzyme. J Biol Chem 278:39960–39968

    Article  PubMed  CAS  Google Scholar 

  100. Vlajkovic SM, Housley GD, Greenwood D, Thorne PR (1999) Evidence for alternative splicing of ecto-ATPase associated with termination of purinergic transmission. Mol Brain Res 73:85–92

    Article  PubMed  CAS  Google Scholar 

  101. Wang CJF, Vlajkovic SM, Housley GD, Braun N, Zimmermann H, Robson SC, Sévigny J, Soeller C, Thorne PR (2005) C-terminal splicing of NTPDase2 provides distinctive catalytic properties, cellular distribution and enzyme regulation. Biochem J 385:729–736

    Article  PubMed  CAS  Google Scholar 

  102. Vlajkovic SM, Wang CJH, Soeller C, Zimmermann H, Thorne PR, Housley GD (2007) Activation-dependent trafficking of NTPDase2 in Chinese hamster ovary cells. Int J Biochem Cell Biol 39:810–817

    Article  PubMed  CAS  Google Scholar 

  103. Chadwick BP, Frischauf AM (1998) The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster. Genomics 50:357–367

    Article  PubMed  CAS  Google Scholar 

  104. Smith TM, Kirley TL (1998) Cloning, sequencing, and expression of a human brain ecto-apyrase related to both the ecto-ATPases and CD39 ecto-apyrases. Biochim Biophys Acta 1386:65–78

    Article  PubMed  CAS  Google Scholar 

  105. Crawford PA, Gaddie KJ, Smith TM, Kirley TL (2007) Characterization of an alternative splice variant of human nucleoside triphosphate diphosphohydrolase 3 (NTPDase3): a possible modulator of nucleotidase activity and purinergic signaling. Arch Biochem Biophys 457:7–15

    Article  PubMed  CAS  Google Scholar 

  106. Biederbick A, Rose S, Elsässer HP (1999) A human intracellular apyrase-like protein, LALP70, localizes to lysosomal/autophagic vacuoles. J Cell Sci 112:2473–2484

    PubMed  CAS  Google Scholar 

  107. Mulero JJ, Yeung G, Nelken ST, Ford JE (1999) CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates. J Biol Chem 29:20064–20067

    Article  Google Scholar 

  108. Hicks-Berger CA, Chadwick BP, Frischauf AM, Kirley TL (2000) Expression and characterization of soluble and membrane-bound human nucleoside triphosphate diphosphohydrolase 6 (CD39L2). J Biol Chem 275:34041–34045

    Article  PubMed  CAS  Google Scholar 

  109. Gao XD, Kaigorodov V, Jigami Y (1999) YND1, a homologue of GDA1, encodes membrane-bound apyrase required for Golgi N- and O-glycosylation in Saccharomyces cerevisiae. J Biol Chem 274:21450–21456

    Article  PubMed  CAS  Google Scholar 

  110. Knowles AF (2009) The single NTPase gene of Drosophila melanogaster encodes an intracellular nucleoside triphosphate diphosphohydrolase 6 (NTPDase6). Arch Biochem Biophys 484:70–79

    Article  PubMed  CAS  Google Scholar 

  111. Read R, Hansen G, Kramer J, Finch R, Li L, Vogel P (2009) Ectonucleoside triphosphate diphosphohydrolase type 5 (Entpd5)-deficient mice develop progressive hepatopathy, hepatocellular tumors, and spermatogenic arrest. Vet Pathol 46:491–504

    Article  PubMed  CAS  Google Scholar 

  112. Velasco JA, Avila MA, Notario V (1999) The product of the cph oncogene is a truncated, nucleotide-binding protein that enhances cellular survival to stress. Oncogene 18:689–701

    Article  PubMed  CAS  Google Scholar 

  113. Smith TM, Carl SAL, Kirley TL (1999) Mutagenesis of two conserved tryptophan residues of the E-type ATPases: inactivation and conversion of an ecto-apyrase to an ecto-NTPase. Biochemistry USA 38:5849–5857

    Article  CAS  Google Scholar 

  114. Grinthal A, Guidotti G (2000) Substitution of His59 converts CD39 apyrase into an ADPase in a quaternary structure dependent manner. Biochemistry USA 39:9–16

    Article  CAS  Google Scholar 

  115. Drosopoulos JHF, Broekman MJ, Islam N, Maliszewski CR, Gayle RB, Marcus AJ (2000) Site-directed mutagenesis of human endothelial cell ecto-ADPase/soluble CD39: requirement of glutamate 174 and serine 218 for enzyme activity and inhibition of platelet recruitment. Biochemistry USA 39:6936–6943

    Article  CAS  Google Scholar 

  116. Yang F, Hicks-Berger CA, Smith TM, Kirley TL (2001) Site-directed mutagenesis of human nucleoside triphosphate diphosphohydrolase 3: the importance of residues in the apyrase conserved regions. Biochemistry USA 40:3943–3950

    Article  CAS  Google Scholar 

  117. Javed R, Yarimizu K, Pelletier N, Li C, Knowles AF (2007) Mutagenesis of lysine 62, asparagine 64, and conserved region 1 reduces the activity of human ecto-ATPase (NTPDase 2). Biochemistry USA 46:6617–6627

    Article  CAS  Google Scholar 

  118. Heine P, Braun N, Sévigny J, Robson SC, Servos J, Zimmermann H (2001) The C-terminal cysteine-rich region dictates specific catalytic properties in chimeras of the ecto-nucleotidases NTPDase1 and NTPDase2. Eur J Biochem 262:102–107

    Article  Google Scholar 

  119. Hicks-Berger CA, Kirley TL (2000) Expression and characterization of human ecto-ATPase and chimeras with CD39 ecto-apyrase. IUBMB Life 50:43–50

    Article  PubMed  CAS  Google Scholar 

  120. Grinthal A, Guidotti G (2002) Transmembrane domains confer different substrate specificities and adenosine diphosphate hydrolysis mechanisms on CD39, CD39L1, and chimeras. Biochemistry USA 41:1947–1956

    Article  CAS  Google Scholar 

  121. Gonzales EB, Kawate T, Gouaux E (2009) Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 460:599–U62

    Article  PubMed  CAS  Google Scholar 

  122. Browne LE, Jiang LH, North RA (2010) New structure enlivens interest in P2X receptors. Trends Pharmacol Sci 31:229–237

    Article  PubMed  CAS  Google Scholar 

  123. Wang TF, Handa M, Guidotti G (1998) Structure and function of ectoapyrase (CD39). Drug Develop Res 45:245–252

    Article  CAS  Google Scholar 

  124. Mukasa T, Lee Y, Knowles AF (2005) Either the carboxyl- or the amino-terminal region of the human ecto-ATPase (E-NTPDase 2) confers detergent and temperature sensitivity to the chicken ecto-ATP-diphosphohydrolase (E-NTPDase 8). Biochemistry USA 44:11160–11170

    Article  CAS  Google Scholar 

  125. Grinthal A, Guidotti G (2006) CD39, NTPDase1, is attached to the plasma membrane by two transmembrane domains. Why? Purinergic Signal 2:391–398

    Article  PubMed  CAS  Google Scholar 

  126. Li CS, Lee Y, Knowles AF (2010) The stability of chicken nucleoside triphosphate diphosphohydrolase 8 requires both of its transmembrane domains. Biochemistry USA 49:134–146

    Article  CAS  Google Scholar 

  127. Papanikolaou A, Papafotika A, Christoforidis S (2011) CD39 reveals novel insights into the role of transmembrane domains in protein processing, apical targeting and activity. Traffic 12:1148–1165

    Article  PubMed  CAS  Google Scholar 

  128. Lemmens R, Kupers L, Sévigny J, Beaudoin AR, Grondin G, Kittel A, Waelkens E, VanDuffel L (2000) Purification, characterization, and localization of an ATP diphosphohydrolase in porcine kidney. Amer J Physiol Renal Physiol 278:F978–F988

    CAS  Google Scholar 

  129. Sørensen CE, Amstrup J, Rasmussen HN, Ankorina-Stark I, Novak I (2003) Rat pancreas secretes particulate ecto-nucleotidase CD39. J Physiol London 551:881–892

    Article  PubMed  CAS  Google Scholar 

  130. Kittel A, Pelletier J, Bigonnesse F, Guckelberger O, Kordas K, Braun N, Robson SC, Sévigny J (2004) Localization of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and NTPDase2 in pancreas and salivary gland. J Histochem Cytochem 52:861–871

    Article  PubMed  CAS  Google Scholar 

  131. Zebisch M, Sträter N (2007) Characterization of rat NTPDase1, -2, and -3 ectodomains refolded from bacterial inclusion bodies. Biochemistry USA 46:11945–11956

    Article  CAS  Google Scholar 

  132. Grinthal A, Guidotti G (2004) Dynamic motions of CD39 transmembrane domains regulate and are regulated by the enzymatic active site. Biochemistry USA 43:13849–13858

    Article  CAS  Google Scholar 

  133. Grinthal A, Guidotti G (2007) Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Biochemistry USA 46:279–290

    Article  CAS  Google Scholar 

  134. Stout JG, Kirley TL (1996) Control of cell membrane ecto-ATPase by oligomerization state: intermolecular cross-linking modulates ATPase activity. Biochemistry USA 35:8289–8298

    Article  CAS  Google Scholar 

  135. Wang TF, Ou Y, Guidotti G (1998) The transmembrane domains of ectoapyrase (CD39) affect its enzymatic activity and quaternary structure. J Biol Chem 273:24814–24821

    Article  PubMed  CAS  Google Scholar 

  136. Failer BU, Aschrafi A, Schmalzing G, Zimmermann H (2003) Determination of native oligomeric state and substrate specificity of rat NTPDase1 and NTPDase2 after heterologous expression in Xenopus oocytes. Eur J Biochem 270:1802–1809

    Article  PubMed  CAS  Google Scholar 

  137. Carl SAL, Smith TM, Kirley TL (1998) Cross-linking induces homodimer formation and inhibits enzymatic activity of chicken stomach ecto-apyrase. Biochem Mol Biol Int 44:463–470

    CAS  Google Scholar 

  138. Smith TM, Kirley TL (1999) Glycosylation is essential for functional expression of a human brain ecto-apyrase. Biochemistry USA 38:1509–1516

    Article  CAS  Google Scholar 

  139. Murphy DM, Ivanenkov VV, Kirley TL (2002) Identification of cysteine residues responsible for oxidative cross-linking and chemical inhibition of human nucleoside-triphosphate diphosphohydrolase 3. J Biol Chem 277:6162–6169

    Article  PubMed  CAS  Google Scholar 

  140. Chiang WC, Knowles AF (2008) Inhibition of human NTPDase 2 by modification of an intramembrane cysteine by p-chloromercuriphenylsulfonate and oxidative cross-linking of the transmembrane domains. Biochemistry USA 47:8775–8785

    Article  CAS  Google Scholar 

  141. Gaddie KJ, Kirley TL (2009) Conserved polar residues stabilize transmembrane domains and promote oligomerization in human nucleoside triphosphate diphosphohydrolase 3. Biochemistry USA 48:9437–9447

    Article  CAS  Google Scholar 

  142. Nicke A, Baumert HG, Rettinger J, Eichele A, Lambrecht G, Mutschler E, Schmalzing G (1998) P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels. EMBO J 17:3016–3028

    Article  PubMed  CAS  Google Scholar 

  143. Bodas E, Aleu J, Pujol G, Martin-Satué M, Marsal J, Solsona C (2000) ATP crossing the cell plasma membrane generates an ionic current in Xenopus oocytes. J Biol Chem 275:20268–20273

    Article  PubMed  CAS  Google Scholar 

  144. Rademacher TW, Parekh RB, Dwek RA (1988) Glycobiology. Annu Rev Biochem 57:785–838

    Article  PubMed  CAS  Google Scholar 

  145. Ivanenkov VV, Meller J, Kirley TL (2005) Characterization of disulfide bonds in human nucleoside triphosphate diphosphohydrolase 3 (NTPDase3): implications for NTPDase structural modeling. Biochemistry USA 44:8998–9012

    Article  CAS  Google Scholar 

  146. Murphy DM, Kirley TL (2003) Asparagine 81, an invariant glycosylation site near apyrase conserved region 1, is essential for full enzymatic activity of ecto-nucleoside triphosphate diphosphohydrolase. Arch Biochem Biophys 419:251–252

    Article  CAS  Google Scholar 

  147. Mulero JJ, Yeung G, Nelken ST, Bright JM, McGowan DW, Ford JE (2000) Biochemical characterization of CD39L4. Biochemistry USA 39:12924–12928

    Article  CAS  Google Scholar 

  148. Murphy-Piedmonte DM, Crawford PA, Kirley TL (2005) Bacterial expression, folding, purification and characterization of soluble NTPDase5 (CD39L4) ecto-nucleotidase. BBA Proteins Proteomics 1747:251–259

    Article  CAS  Google Scholar 

  149. Christoforidis S, Papamarcaki T, Tsolas O (1996) Human placental ATP diphosphohydrolase is a highly N-glycosylated plasma membrane enzyme. BBA Biomem 1282:257–262

    Article  Google Scholar 

  150. Zhong XT, Kriz R, Kumar R, Guidotti G (2005) Distinctive roles of endoplasmic reticulum and Golgi glycosylation in functional surface expression of mammalian E-NTPDasel, CD39. BBA Gen Subjects 1723:143–150

    Article  CAS  Google Scholar 

  151. Wu JJ, Choi LE, Guidotti G (2005) N-linked oligosaccharides affect the enzymatic activity of CD39: diverse interactions between seven N-linked glycosylation sites. Mol Biol Cell 16:1661–1672

    Article  PubMed  CAS  Google Scholar 

  152. Yegutkin GG, Samburski SS, Mortensen SP, Jalkanen S, Gonzalez-Alonso J (2007) Intravascular ADP and soluble nucleotidases contribute to acute prothrombotic state during vigorous exercise in humans. J Physiol 579:553–564

    Article  PubMed  CAS  Google Scholar 

  153. Yegutkin G, Bodin P, Burnstock G (2000) Effect of shear stress on the release of soluble ecto-enzymes ATPase and 5′-nucleotidase along with endogenous ATP from vascular endothelial cells. Brit J Pharmacol 129:921–926

    Article  CAS  Google Scholar 

  154. Ceruti S, Colombo L, Magni G, Vigano F, Boccazzi M, Deli MA, Sperlagh B, Abbracchio MP, Kittel A (2011) Oxygen-glucose deprivation increases the enzymatic activity and the microvesicle-mediated release of ectonucleotidases in the cells composing the blood–brain barrier. Neurochem Int 59:259–271

    Article  PubMed  CAS  Google Scholar 

  155. Beaudoin AR, Vachereau A, Grondin G, St-Jean P, Rosenberg MD, Strobel R (1986) Microvesicular secretion, a mode of cell secretion associated with the presence of an ATP-diphosphohydrolase. FEBS Lett 203:1–2

    Article  PubMed  CAS  Google Scholar 

  156. Yegutkin GG, Samburski SS, Jalkanen S, Novak I (2006) ATP-consuming and ATP-generating enzymes secreted by pancreas. J Biol Chem 281:29441–29447

    Article  PubMed  CAS  Google Scholar 

  157. Kordas KS, Sperlagh B, Tihanyi T, Topa L, Steward MC, Varga G, Kittel A (2004) ATP and ATPase secretion by exocrine pancreas in rat, guinea pig, and human. Pancreas 29:53–60

    Article  PubMed  CAS  Google Scholar 

  158. Banz Y, Beldi G, Wu Y, Atkinson B, Usheva A, Robson SC (2008) CD39 is incorporated into plasma microparticles where it maintains functional properties and impacts endothelial activation. Brit J Haematol 142:627–637

    Article  CAS  Google Scholar 

  159. Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z (2011) Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol 187:676–683

    Article  PubMed  CAS  Google Scholar 

  160. Todorov LD, Mihaylova-Todorova S, Westfall TD, Sneddon P, Kennedy C, Bjur RA, Westfall DP (1997) Neuronal release of soluble nucleotidases and their role in neurotransmitter inactivation. Nature 387:76–79

    Article  PubMed  CAS  Google Scholar 

  161. Westfall DP, Todorov LD, Mihaylova-Todorova ST (2002) ATP as a cotransmitter in sympathetic nerves and its inactivation by releasable enzymes. J Pharmacol Exp Ther 303:439–444

    Article  PubMed  CAS  Google Scholar 

  162. Sterling KM, Shah S, Kim RJ, Johnston NIF, Salikhova AY, Abraham EH (2004) Cystic fibrosis transmembrane conductance regulator in human and mouse red blood cell membranes and its interaction with ecto-apyrase. J Cell Biochem 91:1174–1182

    Article  PubMed  CAS  Google Scholar 

  163. Abraham EH, Sterling KM, Kim RJ, Salikhova AY, Huffman HB, Crockett MA, Johnston N, Parker HW, Boyle WE, Hartov A, Demidenko E, Efird J, Kahn J, Grubman SA, Jefferson DM, Robson SC, Thakar JH, Lorico A, Rappa G, Sartorelli AC, Okunieff P (2001) Erythrocyte membrane ATP binding cassette (ABC) proteins: MRP1 and CFTR as well as CD39 (ecto-apyrase) involved in RBC ATP transport and elevated blood plasma ATP of cystic fibrosis. Blood Cells Molecules Dis 27:165–180

    Article  CAS  Google Scholar 

  164. Schicker K, Hussl S, Chandaka GK, Kosenburger K, Yang JW, Waldhoer M, Sitte HH, Boehm S (2009) A membrane network of receptors and enzymes for adenine nucleotides and nucleosides. BBA Mol Cell Res 1793:325–334

    CAS  Google Scholar 

  165. Alvarado-Castillo C, Lozano-Zarain P, Mateo J, Harden TK, Boyer JL (2002) A fusion protein of the human P2Y1 receptor and NTPDase1 exhibits functional activities of the native receptor and ectoenzyme and reduced signaling. Mol Pharmacol 62:521–528

    Article  PubMed  CAS  Google Scholar 

  166. Wu Y, Sun XF, Kaczmarek E, Dwyer KM, Bianchi E, Usheva A, Robson SC (2006) RanBPM associates with CD39 and modulates ecto-nucleotidase activity. Biochem J 396:23–30

    Article  PubMed  CAS  Google Scholar 

  167. Murrin LC, Talbot JN (2007) RanBPM, a scaffolding protein in the immune and nervous systems. J Neuroimmune Pharmacol 2:290–295

    Article  PubMed  Google Scholar 

  168. Zimmermann H (2006) Ecto-nucleotidases in the nervous system. Novartis Found Symp 275:113–128

    Article  Google Scholar 

  169. Alvarado-Castillo C, Harden TK, Boyer JL (2005) Regulation of P2Y1 receptor-mediated signaling by the ectonucleoside triphosphate diphosphohydrolase isozymes NTPDase1 and NTPDase2. Mol Pharmacol 67:114–122

    Article  PubMed  CAS  Google Scholar 

  170. Kennedy C, Westfall TD, Sneddon P (1996) Modulation of purinergic neurotransmission by ecto-ATPase. Semin Neurosci 8:195–199

    Article  CAS  Google Scholar 

  171. Westfall TD, Kennedy C, Sneddon P (1997) The ecto-ATPase inhibitor ARL 67156 enhances parasympathetic neurotransmission in the guinea-pig urinary bladder. Eur J Pharmacol 329:169–173

    Article  PubMed  CAS  Google Scholar 

  172. Machida T, Heerdt PM, Reid AC, Schäfer U, Silver RB, Broekman MJ, Marcus AJ, Levi R (2005) Ectonucleoside triphosphate diphosphohydrolase1/CD39, localized in neurons of human and porcine heart, modulates ATP-induced norepinephrine exocytosis. J Pharmacol Exp Ther 313:570–577

    Article  PubMed  CAS  Google Scholar 

  173. Ghildyal P, Palani D, Manchanda R (2006) Post- and prejunctional consequences of ecto-ATPase inhibition: electrical and contractile studies in guinea-pig vas deferens. J Physiol London 575:469–480

    Article  PubMed  CAS  Google Scholar 

  174. Goepfert C, Sundberg C, Sévigny J, Enjyoji K, Hoshi T, Csizmadia E, Robson SC (2001) Disordered cellular migration and angiogenesis in cd39-null mice. Circulation 104:3109–3115

    Article  PubMed  CAS  Google Scholar 

  175. Guckelberger O, Sun XF, Sévigny J, Imai M, Kaczmarek E, Enjyoji K, Kruskal JB, Robson SC (2004) Beneficial effects of CD39/ecto-nucleoside triphosphate diphosphohydrolase-I in murine intestinal ischemia-reperfusion injury. Thromb Haemost 91:576–586

    PubMed  CAS  Google Scholar 

  176. Sun XF, Cardenas A, Wu Y, Enjyoji K, Robson SC (2009) Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice. Amer J Physiol Gastrointest L 297:G306–G311

    Article  CAS  Google Scholar 

  177. Levesque SA, Kukulski F, Enjyoji K, Robson SC, Sévigny J (2010) NTPDase1 governs P2X7-dependent functions in murine macrophages. Eur J Immunol 40:1473–1485

    Article  PubMed  CAS  Google Scholar 

  178. Feng LL, Sun XF, Csizmadia E, Han LH, Bian S, Murakami T, Wang X, Robson SC, Wu Y (2011) Vascular CD39/ENTPD1 directly promotes tumor cell growth by scavenging extracellular adenosine triphosphate. Neoplasia 13:206–U34

    PubMed  CAS  Google Scholar 

  179. Dwyer KM, Robson SC, Nandurkar HH, Campbell DJ, Gock H, Murray-Segal LJ, Fisicaro N, Mysore TB, Kaczmarek E, Cowan PJ, D'Apice AJ (2004) Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation. J Clin Invest 113:1440–1446

    PubMed  CAS  Google Scholar 

  180. Furukoji E, Matsumoto M, Yamashita A, Yagi H, Sakurai Y, Marutsuka K, Hatakeyama K, Morishita K, Fujimura Y, Tamura S, Asada Y (2005) Adenovirus-mediated transfer of human placental ectonucleoside triphosphate diphosphohydrolase to vascular smooth muscle cells suppresses platelet aggregation in vitro and arterial thrombus formation in vivo. Circulation 111:808–815

    Article  PubMed  CAS  Google Scholar 

  181. Takemoto Y, Kawata H, Soeda T, Imagawa K, Somekawa S, Takeda Y, Uemura S, Matsumoto M, Fujimura Y, Jo J, Kimura Y, Tabata Y, Saito Y (2009) Human placental ectonucleoside triphosphate diphosphohydrolase gene transfer via gelatin-coated stents prevents in-stent thrombosis. Arterioscler Thromb Vasc Biol 29:857–862

    Article  PubMed  CAS  Google Scholar 

  182. Jhandier MN, Kruglov EA, Lavoie ÉG, Sévigny J, Dranoff JA (2005) Portal fibroblasts regulate the proliferation of bile duct epithelia via expression of NTPDase2. J Biol Chem 280:22986–22992

    Article  PubMed  CAS  Google Scholar 

  183. Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204:1257–1265

    Article  PubMed  CAS  Google Scholar 

  184. Eltzschig HK (2009) Adenosine: an old drug newly discovered. Anesthesiology 111:904–915

    Article  PubMed  CAS  Google Scholar 

  185. Massé K, Eason R, Bhamra S, Dale N, Jones EA (2006) Comparative genomic and expression analysis of the conserved NTPDase gene family in Xenopus. Genomics 87:366–381

    Article  PubMed  CAS  Google Scholar 

  186. Rosemberg DB, Rico EP, Langoni AS, Spinelli JT, Pereira TC, Dias RD, Souza DO, Bonan CD, Bogo MR (2010) NTPDase family in zebrafish: nucleotide hydrolysis, molecular identification and gene expression profiles in brain, liver and heart. Comp Biochem Physiol Pt B 155:230–240

    Article  CAS  Google Scholar 

  187. Burnstock G, Verkhratsky A (2009) Evolutionary origins of the purinergic signalling system. Acta Physiol (Oxf) 195:415–447

    Article  CAS  Google Scholar 

  188. Tanaka K, Gilroy S, Jones AM, Stacey G (2010) Extracellular ATP signaling in plants. Trends Cell Biol 20:601–608

    Article  PubMed  CAS  Google Scholar 

  189. Sansom FM, Robson SC, Hartland EL (2008) Possible effects of microbial ecto-nucleoside triphosphate diphosphohydrolases on host–pathogen interactions. Microbiol Mol Biol Rev 72:765

    Article  PubMed  CAS  Google Scholar 

  190. Buss KA, Cooper DR, Ingram-Smith C, Ferry JG, Sanders DA, Hasson MS (2001) Urkinase: structure of acetate kinase, a member of the ASKHA superfamily of phosphotransferases. J Bacteriol 183:680–686

    Article  PubMed  CAS  Google Scholar 

  191. Flaherty KM, Mckay DB, Kabsch W, Holmes KC (1991) Similarity of the three dimensional structures of actin and the ATPase fragment of a 70-kDa heat shock cognate protein. Proc Natl Acad Sci USA 88:5041–5045

    Article  PubMed  CAS  Google Scholar 

  192. Vorhoff T, Zimmermann H, Pelletier J, Sévigny J, Braun N (2005) Cloning and characterization of the ecto-nucleotidase NTPDase3 from rat brain: predicted secondary structure and relation to members of the E-NTPDase family and actin. Purinergic Signal 1:259–270

    Article  PubMed  CAS  Google Scholar 

  193. Kirley TL, Crawford PA, Smith TM (2006) The structure of the nucleoside triphosphate diphosphohydrolases (NTPDases) as revealed by mutagenic and computational modeling analyses. Purinergic Signal 2:379–389

    Article  PubMed  CAS  Google Scholar 

  194. Ivanenkov VV, Crawford PA, Toyama A, Sévigny J, Kirley TL (2010) Epitope mapping in cell surface proteins by site-directed masking: defining the structural elements of NTPDase3 inhibition by a monoclonal antibody. Protein Eng Des Sel 23:579–588

    Article  PubMed  CAS  Google Scholar 

  195. Zebisch M, Sträter N (2008) Structural insight into signal conversion and inactivation by NTPDase2 in purinergic signaling. Proc Nat Acad Sci USA 105:6882–6887

    Article  PubMed  CAS  Google Scholar 

  196. Vivian JP, Riedmaier P, Ge HH, Le Nours J, Sansom FM, Wilce MCJ, Byres E, Dias M, Schmidberger JW, Cowan PJ, d'Apice AJF, Hartland EL, Rossjohn J, Beddoe T (2010) Crystal structure of a Legionella pneumophila ecto-triphosphate diphosphohydrolase, a structural and functional homolog of the eukaryotic NTPDases. Structure 18:228–238

    Article  PubMed  CAS  Google Scholar 

  197. Gaddie KJ, Kirley TL (2010) Proline residues link the active site to transmembrane domain movements in human nucleoside triphosphate diphosphohydrolase 3 (NTPDase3). Purinergic Signal 6:327–337

    Article  PubMed  CAS  Google Scholar 

  198. Zebisch M, Schäfer P, Krauss M, Sträter N (2012) Crystallographic evidence for a domain motion in rat nucleoside triphosphate diphosphohydrolase (NTPDase) 1. J Mol Biol 15:288–306

    Article  CAS  Google Scholar 

  199. Krug U, Zebisch M, Krauss M, Sträter N (2012) Structural insight into the activation mechanism of Toxoplasma gondii nucleoside triphosphate diphosphohydrolases by disulfide reduction. J Biol Chem 287:3051–66

    Article  PubMed  CAS  Google Scholar 

  200. Garavaglia S, Bruzzone S, Cassani C, Canella L, Allegrone G, Sturla L, Mannino E, Millo E, De FA, Rizzi M (2011) The high-resolution crystal structure of periplasmic Haemophilus influenzae NAD nucleotidase reveals a novel enzymatic function of human CD73 related to NAD metabolism. Biochem J Immediate Publication 441:131–141

    Google Scholar 

  201. Zimmermann H (1992) 5′-Nucleotidase—molecular structure and functional aspects. Biochem J 285:345–365

    PubMed  CAS  Google Scholar 

  202. Hunsucker SA, Mitchell BS, Spychala J (2005) The 5′-nucleotidases as regulators of nucleotide and drug metabolism. Pharmacol Ther 107:1–30

    Article  PubMed  CAS  Google Scholar 

  203. Jin DC, Fan J, Wang L, Thompson LF, Liu AJ, Daniel BJ, Shin T, Curiel TJ, Zhang B (2010) CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. Cancer Res 70:2245–2255

    Article  PubMed  CAS  Google Scholar 

  204. Resta R, Hooker SW, Hansen KR, Laurent AB, Park JL, Blackburn MR, Knudsen TB, Thompson LF (1993) Murine ecto-5′-nucleotidase (CD73)—cDNA cloning and tissue distribution. Gene 133:171–177

    Article  PubMed  CAS  Google Scholar 

  205. Christensen LD (1996) No correlation between CD73 expression and ecto-5′-nucleotidase activity on blood mononuclear cells in vitro—evidence of CD73 (ecto-5′-nucleotidase) on blood mononuclear cells with distinct antigenic properties. APMIS 104:126–134

    Article  PubMed  CAS  Google Scholar 

  206. Navarro JM, Olmo N, Turnay J, López-Conejo MT, Lizarbe MA (1998) Ecto-5′-nucleotidase from a human colon adenocarcinoma cell line. Correlation between enzyme activity and levels in intact cells. Mol Cell Biochem 187:121–131

    Article  PubMed  CAS  Google Scholar 

  207. Garcia-Ayllon MS, Campoy FJ, Vidal CJ, Muñoz-Delgado E (2001) Identification of inactive ecto-5′-nucleotidase in normal mouse muscle and its increased activity in dystrophic Lama2(dy) mice. Neurosci Res 66:656–665

    Article  CAS  Google Scholar 

  208. Morote-Garcia JC, del Campo LFS, Campoy FJ, Vidal CJ, Muñoz-Delgado E (2006) The increased ecto-5′-nucleotidase activity in muscle, heart and liver of laminin alpha 2-deficient mice is not caused by an elevation in the mRNA content. Int J Biochem Cell Biol 38:1092–1101

    Article  PubMed  CAS  Google Scholar 

  209. Naito Y, Lowenstein JM (1981) 5′-Nucleotidase from rat heart. Biochemistry USA 20:5188–5194

    Article  CAS  Google Scholar 

  210. Grondal EJM, Zimmermann H (1987) Purification, characterization and cellular localization of 5′-nucleotidase from Torpedo electric organ. Biochem J 245:805–810

    PubMed  CAS  Google Scholar 

  211. James S, Richardson PJ (1993) Production of adenosine from extracellular ATP at the striatal cholinergic synapse. J Neurochem 60:219–227

    Article  PubMed  CAS  Google Scholar 

  212. Fredholm BB, Ijzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53:527–552

    PubMed  CAS  Google Scholar 

  213. Castrop H, Huang YN, Hashimoto S, Mizel D, Hansen P, Theilig F, Bachmann S, Deng CX, Briggs J, Schnermann J (2004) Impairment of tubuloglomerular feedback regulation of GFR in ecto-5′-nucleotidase/CD73-deficient mice. J Clin Invest 114:634–642

    PubMed  CAS  Google Scholar 

  214. Thompson LF, Eltzschig HK, Ibla JC, Van De Wiele CJ, Resta R, Morote-Garcila JC, Colgan SP (2004) Crucial role for ecto-5′-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200:1395–1405

    Article  PubMed  CAS  Google Scholar 

  215. Koszalka P, Ozuyaman B, Huo YQ, Zernecke A, Flogel U, Braun N, Buchheiser A, Decking UKM, Smith ML, Sévigny J, Gear A, Weber AA, Molojavyi A, Ding ZP, Weber C, Ley K, Zimmermann H, Gödecke A, Schrader J (2004) Targeted disruption of cd73/ecto-5′-nucleotidase alters thromboregulation and augments vascular inflammatory response. Circ Res 95:814–821

    Article  PubMed  CAS  Google Scholar 

  216. El-Tayeb A, Iqbal J, Behrenswerth A, Romio M, Schneider M, Zimmermann H, Schrader J, Müller CE (2009) Nucleoside-5′-monophosphates as prodrugs of adenosine A2A receptor agonists activated by ecto-5′-nucleotidase. J Med Chem 52:7669–7677

    Article  PubMed  CAS  Google Scholar 

  217. Kriz W (2004) Adenosine and ATP: traffic regulators in the kidney. J Clin Invest 114:611–613

    PubMed  CAS  Google Scholar 

  218. Colgan SP, Eltzschig HK, Eckle T, Thompson LF (2006) Physiological roles of ecto-5′-nucleotidase. Purinergic Signal 2:351–360

    Article  PubMed  CAS  Google Scholar 

  219. Schetinger MR, Morsch VM, Bonan CD, Wyse AT (2007) NTPDase and 5′-nucleotidase activities in physiological and disease conditions: new perspectives for human health. Biofactors 31:77–98

    Article  PubMed  CAS  Google Scholar 

  220. Rajakumar SV, Lu B, Crikis S, Robson SC, d'Apice AJF, Cowan PJ, Dwyer KM (2010) Deficiency or inhibition of CD73 protects in mild kidney ischemia-reperfusion injury. Transplantation 90:1260–1264

    Article  PubMed  CAS  Google Scholar 

  221. Robson SC, Schuppan D (2010) Adenosine: tipping the balance towards hepatic steatosis and fibrosis. J Hepatol 52:941–943

    Article  PubMed  CAS  Google Scholar 

  222. Lazarowski ER, Boucher RC (2009) Purinergic receptors in airway epithelia. Curr Opin Pharmacol 9:262–267

    Article  PubMed  CAS  Google Scholar 

  223. Bours MJ, Swennen EL, Di VF, Cronstein BN, Dagnelie PC (2006) Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther 112:358–404

    Article  PubMed  CAS  Google Scholar 

  224. Junger WG (2011) Immune cell regulation by autocrine purinergic signaling. Nature Rev Immunol 11:201–212

    Article  CAS  Google Scholar 

  225. Salmi M, Jalkanen S (2005) Cell-surface enzymes in control of leukocyte trafficking. Nature Rev Immunol 5:760–771

    Article  CAS  Google Scholar 

  226. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55

    Article  PubMed  CAS  Google Scholar 

  227. Dare E, Schulte G, Karovic O, Hammarberg C, Fredholm BB (2007) Modulation of glial cell functions by adenosine receptors. Physiol Behav 92:15–20

    Article  PubMed  CAS  Google Scholar 

  228. Sowa NA, Taylor-Blake B, Zylka MJ (2010) Ecto-5′-nucleotidase (CD73) inhibits nociception by hydrolyzing AMP to adenosine in nociceptive circuits. J Neurosci 30:2235–2244

    Article  PubMed  CAS  Google Scholar 

  229. Spychala J (2000) Tumor-promoting functions of adenosine. Pharmacol Ther 87:161–173

    Article  PubMed  CAS  Google Scholar 

  230. Stagg J, Smyth MJ (2010) Extracellular adenosine triphosphate and adenosine in cancer. Oncogene 29:5346–5358

    Article  PubMed  CAS  Google Scholar 

  231. Zhang B (2010) CD73: a novel target for cancer immunotherapy. Cancer Res 70:6407–6411

    Article  PubMed  CAS  Google Scholar 

  232. Zhi XL, Wang YJ, Zhou XR, Yu J, Jian RR, Tang SX, Yin LH, Zhou P (2010) RNAi-mediated CD73 suppression induces apoptosis and cell-cycle arrest in human breast cancer cells. Cancer Sci 101:2561–2569

    Article  PubMed  CAS  Google Scholar 

  233. Mikhailov A, Sokolovskaya A, Yegutkin GG, Amdahl H, West A, Yagita H, Lahesmaa R, Thompson LF, Jalkanen S, Blokhin D, Eriksson JE (2008) CD73 participates in cellular multiresistance program and protects against TRAIL-induced apoptosis. J Immunol 181:464–475

    PubMed  CAS  Google Scholar 

  234. Stagg J, Divisekera U, Duret H, Sparwasser T, Teng MWL, Darcy PK, Smyth MJ (2011) CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis. Cancer Res 71:2892–2900

    Article  PubMed  CAS  Google Scholar 

  235. Bianchi V, Spychala J (2003) Mammalian 5′-nucleotidases. J Biol Chem 278:46195–46198

    Article  PubMed  CAS  Google Scholar 

  236. Borowiec A, Lechward K, Tkacz-Stachowska K, Skladanowski AC (2006) Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5′-nucleotidases. Acta Biochim Pol 53:269–278

    PubMed  CAS  Google Scholar 

  237. Misumi Y, Ogata S, Hirose S, Ikehara Y (1990) Primary structure of rat liver 5′-nucleotidase deduced from the cDNA. Presence of the COOH-terminal hydrophobic domain for possible post-translational modification by glycophospholipid. J Biol Chem 265:2178–2183

    PubMed  CAS  Google Scholar 

  238. Misumi Y, Ogata S, Ohkubo K, Hirose S, Ikehara Y (1990) Primary structure of human placental 5′-nucleotidase and identification of the glycolipid anchor in the mature form. Eur J Biochem 191:563–569

    Article  PubMed  CAS  Google Scholar 

  239. Volknandt W, Vogel M, Pevsner J, Misumi Y, Ikehara Y, Zimmermann H (1991) 5′-Nucleotidase from the electric ray electric lobe: primary structure and relation to mammalian and procaryotic enzymes. Eur J Biochem 202:855–861

    Article  PubMed  CAS  Google Scholar 

  240. Zimmermann H, Braun N (1999) Ecto-nucleotidases: molecular structures, catalytic properties, and functional roles in the nervous system. Prog Brain Res 120:371–385

    Article  PubMed  CAS  Google Scholar 

  241. Martinez-Martinez A, Muñoz-Delgado E, Campoy FJ, Flores-Flores C, Rodriguez-Lopez JN, Fini C, Vidal CJ (2000) The ecto-5′-nucleotidase subunits in dimers are not linked by disulfide bridges but by non-covalent bonds. Biochim Biophys Acta 1478:300–308

    Article  PubMed  CAS  Google Scholar 

  242. Fini C, Amoresano A, Andolfo A, D'Auria S, Floridi A, Paolini S, Pucci P (2000) Mass spectrometry study of ecto-5′-nucleotidase from bull seminal plasma. Eur J Biochem 267:4978–4987

    Article  PubMed  CAS  Google Scholar 

  243. Servos J, Reiländer H, Zimmermann H (1998) Catalytically active soluble ecto-5′-nucleotidasse purified after heterologous expression as a tool for drug screening. Drug Develop Res 45:269–276

    Article  CAS  Google Scholar 

  244. Sowa NA, Voss MK, Zylka MJ (2010) Recombinant ecto-5′-nucleotidase (CD73) has long lasting antinociceptive effects that are dependent on adenosine A1 receptor activation. Mol Pain 6:20

    Article  PubMed  CAS  Google Scholar 

  245. Suzuki K, Furukawa Y, Tamura H, Ejiri N, Suematsu H, Taguchi R, Nakamura S, Suzuki Y, Ikezawa H (1993) Purification and cDNA cloning of bovine liver 5′- nucleotidase, a GPI-anchored protein, and its expression in COS cells. J Biochem Tokyo 113:607–613

    PubMed  CAS  Google Scholar 

  246. Vogel M, Kowalewski HJ, Zimmermann H, Janetzko A, Margolis RU, Wollny HE (1991) Association of the HNK-1 epitope with 5′-nucleotidase from Torpedo marmorata (electric ray) electric organ. Biochem J 278:199–202

    PubMed  CAS  Google Scholar 

  247. Vogel M, Zimmermann H, Singer W (1993) Transient association of the HNK-1 epitope with 5′-nucleotidase during development of the cat visual cortex. Eur J Neurosci 5:1423–1425

    Article  PubMed  CAS  Google Scholar 

  248. Morote-Garcia JC, Garcia-Ayllón AS, Campoy FJ, Vidal CJ, Muñoz-Delgado E (2004) Active and inactive ecto-5′-nucleotidase variants in liver of control and dystrophic Lama2dy mice. Int J Biochem Cell Biol 36:422–433

    Article  PubMed  CAS  Google Scholar 

  249. Airas L, Niemela J, Salmi M, Puurunen T, Smith DJ, Jalkanen S (1997) Differential regulation and function of CD73, a glycosyl- phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells. J Cell Biol 136:421–431

    Article  PubMed  CAS  Google Scholar 

  250. Chatterjee S, Mayor S (2001) The GPI-anchor and protein sorting. Cell Mol Life Sci 58:1969–1987

    Article  PubMed  CAS  Google Scholar 

  251. Sharom FJ, Lehto MT (2002) Glycosylphosphatidylinositol-anchored proteins: structure, function, and cleavage by phosphatidylinositol-specific phospholipase C. Biochem Cell Biol 80:535–549

    Article  PubMed  CAS  Google Scholar 

  252. Sharom FJ (2010) GPI-anchored proteins: biophysical behaviour and cleavage by PI-specific phospholipases. In: Dangerfield JA, Metzner C (eds) GPI membrane anchors—the much needed link. Bentham Science, Oak Park, pp 34–52

    Chapter  Google Scholar 

  253. Ali N, Evans WH (1990) Priority targeting of glycosyl-phosphatidylinositol-anchored proteins to the bile-canalicular (apical) plasma membrane of hepatocytes. Involvement of ‘late’ endosomes. Biochem J 271:193–199

    PubMed  CAS  Google Scholar 

  254. Ihrke G, Martin GV, Shanks MR, Schrader M, Schroer TA, Hubbard AL (1998) Apical plasma membrane proteins and endolyn-78 travel through a subapical compartment in polarized WIF-B hepatocytes. J Cell Biol 141:115–133

    Article  PubMed  CAS  Google Scholar 

  255. Ogata S, Hayashi Y, Misumi Y, Ikehara Y (1990) Membrane-anchoring domain of rat liver 5′-nucleotidase: identification of the COOH-terminal serine-523 covalently attached with a glycolipid. Biochemistry USA 29:7923–7927

    Article  CAS  Google Scholar 

  256. Furukawa Y, Tamura H, Ikezawa H (1994) Mutational analysis of the COOH-terminal hydrophobic domain of bovine liver 5′-nucleotidase as a signal for glycosylphosphatidylinositol (GPI) anchor attachment. BBA-Biomembranes 1190:273–278

    Article  PubMed  CAS  Google Scholar 

  257. Taguchi R, Hamakawa N, Haradanishida M, Fukui T, Nojima K, Ikezawa H (1994) Microheterogeneity in glycosylphosphatidylinositol anchor structures of bovine liver 5′-nucleotidase. Biochemistry USA 33:1017–1022

    Article  CAS  Google Scholar 

  258. Taguchi R, Hamakawa N, Maekawa N, Ikezawa H (1999) Application of electrospray ionization MS/MS and matrix-assisted laser desorption/ionization-time of flight mass spectrometry to structural analysis of the glycosyl-phosphatidylinositol-anchored protein. J Biochem Tokyo 126:421–429

    Article  PubMed  CAS  Google Scholar 

  259. Kinoshita T, Fujita M, Maeda Y (2008) Biosynthesis, remodelling and functions of mammalian GPI-anchored proteins: recent progress. J Biochem 144:287–294

    Article  PubMed  CAS  Google Scholar 

  260. Sunderman FW Jr (1990) The clinical biochemistry of 5′-nucleotidase. Annu Clin Lab Sci 20:123–139

    Google Scholar 

  261. Johnson SM, Patel S, Bruckner FE, Collins DA (1999) 5′-Nucleotidase as a marker of both general and local inflammation in rheumatoid arthritis patients. Rheumatology (Oxford) 38:391–396

    Article  CAS  Google Scholar 

  262. Chuang NN, Newby AC, Luzio JP (1984) Characterization of different molecular forms of 5′-nucleotidase in normal serum and in serum from cholestatic patients and bile-duct-ligated rats. Biochem J 224:689–695

    PubMed  CAS  Google Scholar 

  263. Fini C, Talamo F, Cherri S, Coli M, Floridi A, Ferrara L, Scaloni A (2003) Biochemical and mass spectrometric characterization of soluble ecto-5′-nucleotidase from bull seminal plasma. Biochem J 372:443–451

    Article  PubMed  CAS  Google Scholar 

  264. Vogel M, Kowalewski H, Zimmermann H, Hooper NM, Turner AJ (1992) Soluble low-K m 5′-nucleotidase from electric ray (Torpedo marmorata) electric organ and bovine cerebral cortex is derived from the glycosyl-phosphatidylinositol-anchored ectoenzyme by phospholipase C cleavage. Biochem J 284:621–624

    PubMed  CAS  Google Scholar 

  265. Trams EG, Lauter CJ, Salem N Jr, Heine U (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645:63–70

    Article  PubMed  CAS  Google Scholar 

  266. Ogawa Y, Murayama N, Yanoshita R (2009) Molecular cloning and characterization of ecto-5′-nucleotidase from the venoms of Gloydius blomhoffi. Toxicon 54:408–412

    Article  PubMed  CAS  Google Scholar 

  267. Müller G, Jung C, Wied S, Biemer-Daub G, Frick W (2010) Transfer of the glycosylphosphatidylinositol-anchored 5′-nucleotidase CD73 from adiposomes into rat adipocytes stimulates lipid synthesis. Brit J Pharmacol 160:878–891

    Article  CAS  Google Scholar 

  268. Airas L, Hellman J, Salmi M, Bono P, Puurunen T, Smith DJ, Jalkanen S (1995) CD73 is involved in lymphocyte binding to the endothelium: characterization of lymphocyte vascular adhesion protein 2 identifies it as CD73. J Exp Med 182:1603–1608

    Article  PubMed  CAS  Google Scholar 

  269. Airas L, Niemela J, Jalkanen S (2000) CD73 engagement promotes lymphocyte binding to endothelial cells via a lymphocyte function-associated antigen-1-dependent mechanism. J Immunol 165:5411–5417

    PubMed  CAS  Google Scholar 

  270. Airas L, Jalkanen S (1996) CD73 mediates adhesion of B cells to follicular dendritic cells. Blood 88:1755–1764

    PubMed  CAS  Google Scholar 

  271. Codogno P, Doyennette-Moyne M-A, Aubery M, Dieckhoff J, Lietzke R, Mannherz HG (1988) Polyclonal and monoclonal antibodies against chicken gizzard 5′-nucleotidase inhibit the spreading process of chicken embryonic fibroblasts on laminin substratum. Exptl Cell Res 174:344–354

    Article  PubMed  CAS  Google Scholar 

  272. Mehul B, Doyennette-Moyne MA, Aubery M, Mannherz HG, Codogno P (1990) 5′-Nucleotidase is involved in chick embryo myoblast spreading on laminin. Cell Biol Int Rep 14:155–164

    Article  PubMed  CAS  Google Scholar 

  273. Stochaj U, Richter H, Mannherz HG (1990) Chicken gizzard 5′-nucleotidase is a receptor for the extracellular matrix component fibronectin. Eur J Cell Biol 51:335–338

    PubMed  CAS  Google Scholar 

  274. Stochaj U, Mannherz HG (1992) Chicken gizzard 5′-nucleotidase functions as a binding protein for the laminin/nidogen complex. Eur J Cell Biol 59:364–372

    PubMed  CAS  Google Scholar 

  275. Olmo N, Turnay J, Risse G, Deutzmann R, von der Mark K, Lizarbe A (1992) Modulation of 5′-nucleotidase activity in plasma membranes and intact cells by the extracellular matrix proteins laminin and fibronectin. Biochem J 282:181–188

    PubMed  CAS  Google Scholar 

  276. Mehul B, Aubery M, Mannherz HG, Codogno P (1993) Dual mechanism of laminin modulation of ecto-5′-nucleotidase activity. J Cell Biochem 52:266–274

    Article  PubMed  CAS  Google Scholar 

  277. Flocke K, Lesch G, Elsässer HP, Bosslet K, Mannherz HG (1992) Monoclonal antibodies against 5′-nucleotidase from a human pancreatic tumor cell line—their characterization and inhibitory capacity on tumor cell adhesion to fibronectin substratum. Eur J Cell Biol 58:62–70

    PubMed  CAS  Google Scholar 

  278. Sadej R, Inail K, Rajfur Z, Ostapkowicz A, Kohler J, Skladanowski AC, Mitchell BS, Spychala J (2008) Tenascin C interacts with ecto-5′-nucleotidase (EN) and regulates adenosine generation in cancer cells. BBA Mol Basis Dis 1782:35–40

    Article  CAS  Google Scholar 

  279. Dianzani U, Redoglia V, Bragardo M, Attisano C, Bianchi A, Difranco D, Ramenghi U, Wolff H, Thompson LF, Pileri A, Massaia M (1993) Co-stimulatory signal delivered by CD73 molecule to human CD45RAhiCD45ROlo (naive) CD8+ T lymphocytes. J Immunol 151:3961–3970

    PubMed  CAS  Google Scholar 

  280. Thompson LF, Ruedi JM, Glass A, Low MG, Lucas AH (1989) Antibodies to 5′-nucleotidase (CD73), a glycosyl-phosphatidylinositol-anchored protein, cause human peripheral blood T cells to proliferate. J Immunol 143:1815–1821

    PubMed  CAS  Google Scholar 

  281. Massaia M, Perrin L, Bianchi A, Ruedi J, Attisano C, Altieri D, Rijkers GT, Thompson LF (1990) Human T cell activation. Synergy between CD73 (ecto-5′-nucleotidase) and signals delivered through CD3 and CD2 molecules. J Immunol 145:1664–1674

    PubMed  CAS  Google Scholar 

  282. Resta R, Hooker SW, Laurent AB, Shuck JK, Misumi Y, Ikehara Y, Koretzky GA, Thompson LF (1994) Glycosyl phosphatidylinositol membrane anchor is not required for T cell activation through CD73. J Immunol 153:1046–1053

    PubMed  CAS  Google Scholar 

  283. Gutensohn W, Resta R, Misumi Y, Ikehara Y, Thompson LF (1995) Ecto-5′-nucleotidase activity is not required for T cell activation through CD73. Cell Immunol 161:213–217

    Article  PubMed  CAS  Google Scholar 

  284. Resta R, Thompson LF (1997) T cell signalling through CD73. Cell Signal 9:131–139

    Article  PubMed  CAS  Google Scholar 

  285. Airas L (1998) CD73 and adhesion of B-cells to follicular dendritic cells. Leuk Lymphoma 29:37–47

    Article  PubMed  CAS  Google Scholar 

  286. Resta R, Yamashita Y, Thompson LF (1998) Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev 161:95–109

    Article  PubMed  CAS  Google Scholar 

  287. Sharom FJ, Radeva G (2004) GPI-anchored protein cleavage in the regulation of transmembrane signals. In: Quinn PJ (ed) Membrane dynamics and domains. Kluwer Academic/Plenum, New York, pp 295–315

    Google Scholar 

  288. Fujita M, Jigami Y (2008) Lipid remodeling of GPI-anchored proteins and its function. Biochim Biophys Acta 1780:410–420

    Article  PubMed  CAS  Google Scholar 

  289. Zhuo S, Clemens JC, Stone RL, Dixon JE (1994) Mutational analysis of a Ser/Thr phosphatase—identification of residues important in phosphoesterase substrate binding and catalysis. J Biol Chem 269:26234–26238

    PubMed  CAS  Google Scholar 

  290. Zimmermann H (1996) Extracellular purine metabolism. Drug Develop Res 39:337–352

    Article  CAS  Google Scholar 

  291. Glaser L, Melo A, Paul R (1967) Uridine diphosphate sugar hydrolase. Purification of enzyme and protein inhibitor. J Biol Chem 242:1944–1954

    PubMed  CAS  Google Scholar 

  292. Neu HC (1968) The 5′-nucleotidases (uridine diphosphate sugar hydrolases) of the Enterobacteriaceae. Biochemistry USA 7:3766–3773

    Article  CAS  Google Scholar 

  293. Champagne DE, Smartt CT, Ribeiro JMC, James AA (1995) The salivary gland-specific apyrase of the mosquito Aedes aegypti is a member of the 5′-nucleotidase family. Proc Natl Acad Sci USA 92:694–698

    Article  PubMed  CAS  Google Scholar 

  294. Lombardo F, Di Cristina M, Spanos L, Louis C, Coluzzi M, Arca B (2000) Promoter sequences of the putative Anopheles gambiae apyrase confer salivary gland expression in Drosophila melanogaster. J Biol Chem 275:23861–23868

    Article  PubMed  CAS  Google Scholar 

  295. Faudry E, Lozzi SP, Santana JM, D'Souza-Ault M, Kieffer S, Felix CR, Ricart CA, Sousa MV, Vernet T, Teixeira AR (2004) Triatoma infestans apyrases belong to the 5′-nucleotidase family. J Biol Chem 279:19607–19613

    Article  PubMed  CAS  Google Scholar 

  296. Charlab R, Valenzuela JG, Rowton ED, Ribeiro JMC (1999) Toward an understanding of the biochemical and pharmacological complexity of the saliva of a hematophagous sand fly Lutzomyia longipalpis. Proc Nat Acad Sci USA 96:15155–15160

    Article  PubMed  CAS  Google Scholar 

  297. Stutzer C, Mans BJ, Gaspar ARM, Neitz AWH, Maritz-Olivier C (2009) Ornithodoros savignyi: soft tick apyrase belongs to the 5′-nucleotidase family. Exp Parasitol 122:318–327

    Article  PubMed  CAS  Google Scholar 

  298. Koonin EV (1994) Conserved sequence pattern in a wide variety of phosphoesterases. Protein Sci 3:356–358

    Article  PubMed  CAS  Google Scholar 

  299. Sträter N, Klabunde T, Tucker P, Witzel H, Krebs B (1995) Crystal structure of a purple acid phosphatase containing a dinuclear Fe(III)–Zn(II) active site. Science 268:1489–1492

    Article  PubMed  Google Scholar 

  300. Knöfel T, Sträter N (1999) X-ray structure of the Escherichia coli periplasmic 5′-nucleotidase containing a dimetal catalytic site. Nature Struct Biol 6:448–453

    Article  PubMed  Google Scholar 

  301. Knöfel T, Sträter N (2001) Mechanism of hydrolysis of phosphate esters by the dimetal center of 5′-nucleotidase based on crystal structures. J Mol Biol 309:239–254

    Article  PubMed  CAS  Google Scholar 

  302. Knöfel T, Sträter N (2001) E-coli 5′-nucleotidase undergoes a hinge-bending domain rotation resembling a ball-and-socket motion. J Mol Biol 309:255–266

    Article  PubMed  CAS  Google Scholar 

  303. Schultz-Heienbrok R, Maier T, Sträter N (2004) Trapping a 96 degrees domain rotation in two distinct conformations by engineered disulfide bridges. Protein Sci 13:1811–1822

    Article  PubMed  CAS  Google Scholar 

  304. Schultz-Heienbrok R, Maier T, Sträter N (2005) A large hinge bending domain rotation is necessary for the catalytic function of Escherichia coli 5′-nucleotidase. Biochemistry USA 44:2244–2252

    Article  CAS  Google Scholar 

  305. Neu HC (1967) The 5′-nucleotidase of Escherichia coli. I. Purification and properties. J Biol Chem 242:3896–3904

    PubMed  CAS  Google Scholar 

  306. Dvorak HF, Heppel LA (1968) Metallo-enzymes released from Escherichia coli by osmotic shock. II. Evidence that 5′-nucleotidase and cyclic phosphodiesterase are zinc metallo-enzymes. J Biol Chem 243:2647–2653

    PubMed  CAS  Google Scholar 

  307. McMillen L, Beacham IR, Burns DM (2003) Cobalt activation of Escherichia coli 5′-nucleotidase is due to zinc ion displacement at only one of two metal-ion-binding sites. Biochem J 372:625–630

    Article  PubMed  CAS  Google Scholar 

  308. Sträter N (2006) Ecto-5′-nucleotidase: structure function relationships. Purinergic Signal 2:343–350

    Article  PubMed  CAS  Google Scholar 

  309. Klabunde T, Sträter N, Fröhlich R, Witzel H, Krebs B (1996) Mechanism of Fe(III)–Zn(II) purple acid phosphatase based on crystal structures. J Mol Biol 259:737–748

    Article  PubMed  CAS  Google Scholar 

  310. Mueller EG, Crowder MA, Averill BA, Knowles JR (1993) Purple acid phosphatase: a diiron enzyme that catalyzes a direct phospho group transfer to water. J Am Chem Soc 115:2974–2975

    Article  CAS  Google Scholar 

  311. Sträter N (2004) 5′-Nucleotidase. In: Messerschmidt A, Bode W, Cygler M (eds) Handbook of metalloproteins. Wiley, Chichester, pp 62–70

    Google Scholar 

  312. Stefan C, Jansen S, Bollen M (2006) Modulation of purinergic signaling by NNP-type ectophosphodiesterases. Purinergic Signal 2:361–370

    Article  PubMed  CAS  Google Scholar 

  313. Stefan C, Gijsbers R, Stalmans W, Bollen M (1999) Differential regulation of the expression of nucleotide pyrophosphatases/phosphodiesterases in rat liver. Biochim Biophys Acta 1450:45–52

    Article  PubMed  CAS  Google Scholar 

  314. Vaingankar SM, Fitzpatrick TA, Johnson K, Goding JW, Maurice M, Terkeltaub R (2004) Subcellular targeting and function of osteoblast nucleotide pyrophosphatase phosphodiesterase 1. Amer J Physiol Cell Physiol 286:C1177–C1187

    Article  CAS  Google Scholar 

  315. Picher M, Boucher RC (2000) Biochemical evidence for an ecto-alkaline phosphodiesterase I in human airways. Amer J Respir Cell Molec Biol 23:255–261

    CAS  Google Scholar 

  316. Vekaria RM, Shirley DG, Sévigny J, Unwin RJ (2006) Immunolocalization of ectonucleotidases along the rat nephron. Amer J Physiol Renal Physiol 290:F550–F560

    Article  CAS  Google Scholar 

  317. Scott LJ, Delautier D, Meerson NR, Trugnan G, Goding JW, Maurice M (1997) Biochemical and molecular identification of distinct forms of alkaline phosphodiesterase I expressed on the apical and basolateral plasma membrane surfaces of rat hepatocytes. Hepatol 25:995–1002

    Article  CAS  Google Scholar 

  318. Murabe Y, Sano Y (1981) Thiaminepyrophosphatase activity in the plasma membrane of microglia. Histochemistry 71:45–52

    Article  PubMed  CAS  Google Scholar 

  319. Langer D, Hammer K, Koszalka P, Schrader J, Robson S, Zimmermann H (2008) Distribution of ectonucleotidases in the rodent brain revisited. Cell Tissue Res 334:199–217

    Article  PubMed  CAS  Google Scholar 

  320. Aoki J (2004) Mechanisms of lysophosphatidic acid production. Semin Cell Dev Biol 15:477–489

    Article  PubMed  CAS  Google Scholar 

  321. Sato K, Malchinkhuu E, Muraki T, Ishikawa K, Hayashi K, Tosaka M, Mochiduki A, Inoue K, Tomura H, Mogi C, Nochi H, Tamoto K, Okajima F (2005) Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources. J Neurochem 92:904–914

    Article  PubMed  CAS  Google Scholar 

  322. Ohuchi H, Hayashibara Y, Matsuda H, Onoi M, Mitsumori M, Tanaka M, Aoki J, Arai H, Noji S (2007) Diversified expression patterns of autotaxin, a gene for phospholipid-generating enzyme during mouse and chicken development. Develop Dynam 236:1134–1143

    Article  CAS  Google Scholar 

  323. Koike S, Yutoh Y, Keino-Masu K, Noji S, Masu M, Ohuchi H (2011) Autotaxin is required for the cranial neural tube closure and establishment of the midbrain-hindbrain boundary during mouse development. Develop Dynam 240:413–421

    Article  Google Scholar 

  324. Anderson KC, Bates MP, Slaughenhoupt B, Schlossman SF, Nadler LM (1984) A monoclonal antibody with reactivity restricted to normal and neoplastic plasma cells. J Immunol 132:3172–3179

    PubMed  CAS  Google Scholar 

  325. Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM (1984) Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood 63:1424–1433

    PubMed  CAS  Google Scholar 

  326. Deterre P, Gelman L, Gary-Gouy H, Arrieumerlou C, Berthelier V, Tixier EM, Ktorza S, Goding L, Schmitt C, Bismuth G (1996) Coordinated regulation in human T cells of nucleotide-hydrolyzing ecto-enzymatic activities, including CD38 and PC-1—possible role in the recycling of nicotinamide adenine dinucleotide metabolites. J Immunol 157:1381–1388

    PubMed  CAS  Google Scholar 

  327. Aerts I, Martin JJ, De Deyn PP, Van Ginniken C, Van Ostade X, Kockx M, Dua G, Slegers H (2011) The expression of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (E-NPP1) is correlated with astrocytic tumor grade. Clin Neurol Neurosurg 113:224–229

    Article  PubMed  Google Scholar 

  328. Prosdocimo DA, Wyler SC, Romani AM, ONeill WC, Dubyak GR (2010) Regulation of vascular smooth muscle cell calcification by extracellular pyrophosphate homeostasis: synergistic modulation by cyclic AMP and hyperphosphatemia. Amer J Physiol Cell Physiol 298:C702–C713

    Article  CAS  Google Scholar 

  329. Johnson K, Terkeltaub R (2005) Inorganic pyrophosphate (PPI) in pathologic calcification of articular cartilage. Front Biosci 10:988–997

    Article  PubMed  CAS  Google Scholar 

  330. Orimo H (2010) The mechanism of mineralization and the role of alkaline phosphatase in health and disease. J Nippon Med Sch 77:4–12

    Article  CAS  Google Scholar 

  331. Goding JW, Grobben B, Slegers H (2003) Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. BBA Mol Basis Dis 1638:1–19

    Article  CAS  Google Scholar 

  332. Anderson HC, Harmey D, Camacho NP, Garimella R, Sipe JB, Tague S, Bi XH, Johnson K, Terkeltaub R, Millán JL (2005) Sustained osteomalacia of long bones despite major improvement in other hypophosphatasia-related mineral deficits in tissue nonspecific alkaline phosphatase/nucleotide pyrophosphatase phosphodiesterase 1 double-deficient mice. Amer J Pathol 166:1711–1720

    Article  CAS  Google Scholar 

  333. Terkeltaub R (2006) Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing in calcification. Purinergic Signal 2:371–377

    Article  PubMed  CAS  Google Scholar 

  334. Stefan C, Jansen S, Bollen M (2005) NPP-type ectophosphodiesterases: unity in diversity. Trends Biochem Sci 30:542–550

    Article  PubMed  CAS  Google Scholar 

  335. Abate N, Chandalia M, Di PR, Foster DW, Grundy SM, Trischitta V (2006) Mechanisms of disease: ectonucleotide pyrophosphatase phosphodiesterase 1 as a ‘gatekeeper’ of insulin receptors. Nat Clin Pract Endocrinol Metab 2:694–701

    Article  PubMed  CAS  Google Scholar 

  336. Goldfine ID, Maddux BA, Youngren JF, Reaven G, Accili D, Trischitta V, Vigneri R, Frittitta L (2008) The role of membrane glycoprotein plasma cell antigen 1 ectonucleotide pyrophosphatase phosphodiesterase 1 in the pathogenesis of insulin resistance and related abnormalities. Endocrine Rev 29:62–75

    Article  CAS  Google Scholar 

  337. Deissler H, Blass-Kampmann S, Bruyneel E, Mareel M, Rajewsky MF (1999) Neural cell surface differentiation antigen gp130RB13-6 induces fibroblasts and glioma cells to express astroglial proteins and invasive properties. FASEB J 13:657–666

    PubMed  CAS  Google Scholar 

  338. Buhring HJ, Seiffert M, Giesert C, Marxer A, Kanz L, Valent P, Sano K (2001) The basophil activation marker defined by antibody 97A6 is identical to the ectonucleotide pyrophosphatase/phosphodiesterase. Blood 97:3303–3305

    Article  PubMed  CAS  Google Scholar 

  339. Buhring HJ, Streble A, Valent P (2004) The basophil-specific ectoenzyme E-NPP3 (CD203c) as a marker for cell activation and allergy diagnosis. Int Arch Allergy Immunol 133:317–329

    Article  PubMed  CAS  Google Scholar 

  340. Hauswirth AW, Sonneck K, Florian S, Krauth MT, Bohm A, Sperr WR, Valenta R, Schernthaner GH, Printz D, Fritsch G, Buhring HJ, Valent P (2007) Interleukin-3 promotes the expression of E-NPP3/CD203C on human blood basophils in healthy subjects and in patients with birch pollen allergy. Int J Immunopathol Pharmacol 20:267–278

    PubMed  CAS  Google Scholar 

  341. Hauswirth AW, Escribano L, Prados A, Nunez R, Mirkina I, Kneidinger M, Florian S, Sonneck K, Vales A, Schernthaner GH, Sanchez-Munoz L, Sperr WR, Buhring HJ, Orfao A, Valent P (2008) CD203c is overexpressed on neoplastic mast cells in systemic mastocytosis and is upregulated upon IgE receptor cross-linking. Int J Immunopathol Pharmacol 21:797–806

    PubMed  CAS  Google Scholar 

  342. Hausmann OV, Gentinetta T, Bridts CH, Ebo DG (2009) The basophil activation test in immediate-type drug allergy. Immunol Allergy Clin North Am 29:555–566

    Article  PubMed  Google Scholar 

  343. van Meeteren LA, Moolenaar WH (2007) Regulation and biological activities of the autotaxin-LPA axis. Prog Lipid Res 46:145–160

    Article  PubMed  CAS  Google Scholar 

  344. Boutin JA, Ferry G (2009) Autotaxin. Cell Mol Life Sci 66:3009–3021

    Article  PubMed  CAS  Google Scholar 

  345. Moolenaar WH, Perrakis A (2011) Insights into autotaxin: how to produce and present a lipid mediator. Nat Rev Mol Cell Biol 12:674–679

    Article  PubMed  CAS  Google Scholar 

  346. Fuss B, Baba H, Phan T, Tuohy VK, Macklin WB (1997) Phosphodiesterase I, a novel adhesion molecule and/or cytokine involved in oligodendrocyte function. J Neurosci 17:9095–9103

    PubMed  CAS  Google Scholar 

  347. Dennis J, Nogaroli L, Fuss B (2005) Phosphodiesterase-Iα/autotaxin (PD-Iα/ATX): a multifunctional protein involved in central nervous system development. J Neurosci Res 82:737–742

    Article  PubMed  CAS  Google Scholar 

  348. Yuelling LM, Fuss B (2008) Autotaxin (ADX): a multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties. BBA Mol Cell Biol Lipids 1781:525–530

    CAS  Google Scholar 

  349. Sela BA, Lis H, Sachs L (1972) Enzymatic hydrolysis of uridine diphosphate-N-acetyl-D-galactosamine and uridine diphospate-N-acetyl-d-glucosamine by normal cells, and blocks in this hydrolysis in transformed cells and their revertants. J Biol Chem 247:7585–7590

    PubMed  CAS  Google Scholar 

  350. Evans WH, Hood DO, Gurd JW (1973) Purification and properties of a mouse liver plasma-membrane glycoprotein hydrolysing nucleotide pyrophosphate and phosphodiester bonds. Biochem J 135:819–826

    PubMed  CAS  Google Scholar 

  351. Vollmayer P, Clair T, Goding JW, Sano K, Servos J, Zimmermann H (2003) Hydrolysis of diadenosine polyphosphates by nucleotide pyrophosphatases/phosphodiesterases. Eur J Biochem 270:2971–2978

    Article  PubMed  CAS  Google Scholar 

  352. Asensio AC, Rodríguez-Ferrera CR, Castañeyra-Perdomo A, Oaknin S, Rotllán P (2007) Biochemical analysis of ecto-nucleotide pyrophosphatase phosphodiesterase activity in brain membranes indicates involvement of NPP1 isoenzyme in extracellular hydrolysis of diadenosine polyphosphates in central nervous system. Neurochem Int 50:581–590

    Article  PubMed  CAS  Google Scholar 

  353. Gijsbers R, Aoki J, Arai H, Bollen M (2003) The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site. FEBS Lett 538:60–64

    Article  PubMed  CAS  Google Scholar 

  354. Kelly SJ, Dardinger DE, Butler LG (1975) Hydrolysis of phosphonate esters catalyzed by 5′-nucleotide phosphodiesterase. Biochemistry USA 14:4983–4988

    Article  CAS  Google Scholar 

  355. Kelly SJ, Butler LG (1977) Enzymic hydrolysis of phosphonate esters. Reaction mechanism of intestinal 5′-nucleotide phosphodiesterase. Biochemistry USA 16:1102–1104

    Article  CAS  Google Scholar 

  356. Landt M, Butler LG (1978) 5′-Nucleotide phosphodiesterase: isolation of covalently bound 5′-adenosine monophosphate, an intermediate in the catalytic mechanism. Biochemistry USA 17:4130–4135

    Article  CAS  Google Scholar 

  357. Landt M, Everard RA, Butler LG (1980) 5′-Nucleotide phosphodiesterase: features of the substrate binding site as deduced from specificity and kinetics of some novel substrates. Biochemistry USA 19:138–143

    Article  CAS  Google Scholar 

  358. Chiavegatti T, Costa VL, Araujo MS, Godinho RO (2008) Skeletal muscle expresses the extracellular cyclic AMP–adenosine pathway. Brit J Pharmacol 153:1331–1340

    Article  CAS  Google Scholar 

  359. Giron MC, Bin A, Brun P, Etteri S, Bolego C, Florio C, Gaion RM (2008) Cyclic AMP in rat ileum: evidence for the presence of an extracellular cyclic AMP–adenosine pathway. Gastroenterology 134:1116–1126

    Article  PubMed  CAS  Google Scholar 

  360. Bischoff E, Tran-Thi TA, Decker KF (1975) Nucleotide pyrophosphatase of rat liver. A comparative study on the enzymes solubilized and purified from plasma membrane and endoplasmic reticulum. Eur J Biochem 51:353–361

    Article  PubMed  CAS  Google Scholar 

  361. Moe OA Jr, Butler LG (1983) The catalytic mechanism of bovine intestinal 5′-nucleotide phosphodiesterase. pH and inhibition studies. J Biol Chem 258:6941–6946

    PubMed  CAS  Google Scholar 

  362. Ciancaglini P, Yadav MC, Simão AMS, Narisawa S, Pizauro JM, Farquharson C, Hoylaerts MF, Millán JL (2010) Kinetic analysis of substrate utilization by native and TNAP-, NPP1-, or PHOSPHO1-deficient matrix vesicles. J Bone Miner Res 25:716–723

    PubMed  CAS  Google Scholar 

  363. Simão AM, Yadav MC, Narisawa S, Bolean M, Pizauro JM, Hoylaerts MF, Ciancaglini P, Millán JL (2010) Proteoliposomes harboring alkaline phosphatase and nucleotide pyrophosphatase as matrix vesicle biomimetics. J Biol Chem 285:7598–7609

    Article  PubMed  CAS  Google Scholar 

  364. Clair T, Lee HY, Liotta LA, Stracke ML (1997) Autotaxin is an exoenzyme possessing 5′-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. J Biol Chem 272:996–1001

    Article  PubMed  CAS  Google Scholar 

  365. Hosoda N, Hoshino S, Kanda Y, Katada T (1999) Inhibition of phosphodiesterase/pyrophosphatase activity of PC-1 by its association with glycosaminoglycans. Eur J Biochem 265:763–770

    Article  PubMed  CAS  Google Scholar 

  366. Bollen M, Gijsbers R, Ceulemans H, Stalmans W, Stefan C (2000) Nucleotide pyrophosphatases/phosphodiesterases on the move. Crit Rev Biochem Molec Biol 35:393–432

    Article  CAS  Google Scholar 

  367. Gijsbers R, Ceulemans H, Stalmans W, Bollen M (2001) Structural and catalytic similarities between nucleotide pyrophosphatases/phosphodiesterases and alkaline phosphatases. J Biol Chem 276:1361–1368

    Article  PubMed  CAS  Google Scholar 

  368. Wojcik M, Cieslak M, Stec WJ, Goding JW, Koziolkiewicz M (2007) Nucleotide pyrophosphatase/phosphodiesterase 1 is responsible for degradation of antisense phosphorothioate oligonucleotides. Oligonucleotides 17:134–145

    Article  PubMed  CAS  Google Scholar 

  369. Grobben B, Anciaux K, Roymans D, Stefan C, Bollen M, Esmans EL, Slegers H (1999) An ecto-nucleotide pyrophosphatase is one of the main enzymes involved in the extracellular metabolism of ATP in rat C6 glioma. J Neurochem 72:826–834

    Article  PubMed  CAS  Google Scholar 

  370. Ramos A, Pintor J, Miras-Portugal MT, Rotllán P (1995) Use of fluorogenic substrates for detection and investigation of ectoenzymatic hydrolysis of diadenosine polyphosphates: a fluorometric study on chromaffin cells. Anal Biochem 228:74–82

    Article  PubMed  CAS  Google Scholar 

  371. Gasmi L, Cartwright JL, McLennan AG (1998) The hydrolytic activity of bovine adrenal medullary plasma membranes towards diadenosine polyphosphates is due to alkaline phosphodiesterase-I. Biochim Biophys Acta 1405:121–127

    Article  PubMed  CAS  Google Scholar 

  372. Lüthje J, Ogilvie A (1987) Catabolism of AP4A and Ap3A in human serum. Identification of isoenzymes and their partial characterization. Eur J Biochem 169:385–388

    Article  PubMed  Google Scholar 

  373. Rotllán P, Asensio AC, Ramos A, Rodríguez-Ferrer CR, Oaknin S (2002) Ectoenzymatic hydrolysis of the signaling nucleotides diadenosine polyphoaphates. In: Recent research developments in Biochemistry, vol. 3. Trivandrum, India: Research Signpos, pp 191–209

  374. Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K (2002) Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 277:39436–39442

    Article  PubMed  CAS  Google Scholar 

  375. Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H (2002) Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 158:227–233

    Article  PubMed  CAS  Google Scholar 

  376. Cimpean A, Stefan C, Gijsbers R, Stalmans W, Bollen M (2004) Substrate-specifying determinants of the nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2. Biochem J 381:71–77

    Article  PubMed  CAS  Google Scholar 

  377. Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, Mizuno K, Saku K, Taguchi R, Arai H (2002) Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem 277:48737–48744

    Article  PubMed  CAS  Google Scholar 

  378. Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M, Noji S, Yatomi Y, Aoki J, Arai H (2006) Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J Biol Chem 281:25822–25830

    Article  PubMed  CAS  Google Scholar 

  379. vanMeeteren LA, Ruurs P, Stortelers C, Bouwman P, vanRooijen MA, Pradere JP, Pettit TR, Wakelam MJO, SaulnierBlache JS, Mummery CL, Moolenaar WH, Jonkers J (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26:5015–5022

    Article  CAS  Google Scholar 

  380. Clair T, Aoki J, Koh E, Bandle RW, Nam SW, Ptaszynska MM, Mills GB, Schiffmann E, Liotta LA, Stracke ML (2003) Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate. Cancer Res 63:5446–5453

    PubMed  CAS  Google Scholar 

  381. van Meeteren LA, Ruurs P, Christodoulou E, Goding JW, Takakusa H, Kikuchi K, Perrakis A, Nagano T, Moolenaar WH (2005) Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. J Biol Chem 280:21155–21161

    Article  PubMed  CAS  Google Scholar 

  382. Tsuda S, Okudaira S, Moriya-Ito K, Shimamoto C, Tanaka M, Aoki J, Arai H, Murakami-Murofushi K, Kobayashi T (2006) Cyclic phosphatidic acid is produced by autotaxin in blood. J Biol Chem 281:26081–26088

    Article  PubMed  CAS  Google Scholar 

  383. Fujiwara Y (2008) Cyclic phosphatidic acid—a unique bioactive phospholipid. Biochim Biophys Acta 1781:519–524

    PubMed  CAS  Google Scholar 

  384. Koh E, Clair T, Woodhouse EC, Schiffmann E, Liotta L, Stracke M (2003) Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities. Cancer Res 63:2042–2045

    PubMed  CAS  Google Scholar 

  385. Hama K, Aoki J, Fukaya M, Kishi Y, Sakai T, Suzuki R (2004) Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA(1). J Biol Chem 279:17634–17639

    Article  PubMed  CAS  Google Scholar 

  386. Kishi Y, Okudaira S, Tanaka M, Hama K, Shida D, Kitayama J, Yamori T, Aoki J, Fujimaki T, Arai H (2006) Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem 281:17492–17500

    Article  PubMed  CAS  Google Scholar 

  387. Luquain C, Sciorra VA, Morris AJ (2003) Lysophosphatidic acid signaling: how a small lipid does big things. Trends Biochem Sci 28:377–383

    Article  PubMed  CAS  Google Scholar 

  388. Sakagami H, Aoki J, Natori Y, Nishikawa K, Kakehi Y, Arai H (2005) Biochemical and molecular characterization of a novel choline-specific glycerophosphodiester phosphodiesterase belonging to the nucleotide pyrophosphatase/phosphodiesterase family. J Biol Chem 280:23084–23093

    Article  PubMed  CAS  Google Scholar 

  389. Duan RD, Bergman T, Xu N, Wu J, Cheng Y, Duan JX, Nelander S, Palmberg C, Nilsson A (2003) Identification of human intestinal alkaline sphingomyelinase as a novel ecto-enzyme related to the nucleotide phosphodiesterase family. J Biol Chem 278:38528–38536

    Article  PubMed  CAS  Google Scholar 

  390. Zhang Y, Cheng YJ, Hansen GH, Niels-Christiansen LL, Koentgen F, Ohlsson L, Nilsson A, Duan RD (2011) Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on enzyme knockout mice. J Lipid Res 52:771–781

    Article  PubMed  CAS  Google Scholar 

  391. Wu J, Nilsson A, Jonsson BA, Stenstad H, Agace W, Cheng Y, Duan RD (2006) Intestinal alkaline sphingomyelinase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity. Biochem J 394:299–308

    Article  PubMed  CAS  Google Scholar 

  392. Takahashi T, Old LJ, Boyse EA (1970) Surface alloantigens of plasma cells. J Exp Med 131:1325–1341

    Article  PubMed  CAS  Google Scholar 

  393. Goding JW, Shen FW (1982) Structure of the murine plasma cell alloantigen PC-1: comparison with the receptor for transferring. J Immunol 129:2636–2640

    PubMed  CAS  Google Scholar 

  394. van Driel IR, Wilks AF, Pietersz GA, Goding JW (1985) Murine plasma cell membrane antigen PC-1: molecular cloning of cDNA and analysis of expression. Proc Natl Acad Sci USA 82:8619–8623

    Article  PubMed  Google Scholar 

  395. van Driel IR, Goding JW (1987) Plasma cell membrane gylcoprotein PC-1: primary structure deduced from cDNA clones. J Biol Chem 262:4882–4887

    PubMed  Google Scholar 

  396. Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW (1990) Plasma membrane glycoprotein PC-1: cDNA cloning of the human molecule, amino acid sequence and chromosomal location. J Biol Chem 265:17506–17511

    PubMed  CAS  Google Scholar 

  397. Belli SI, Goding JW (1994) Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphate activities. Eur J Biochem 226:433–443

    Article  PubMed  CAS  Google Scholar 

  398. Deissler H, Lottspeich F, Rajewsky MF (1995) Affinity purification and cDNA cloning of rat neural differentiation and tumor cell surface antigen gp130RB13-6 reveals relationship to human and murine PC-1. J Biol Chem 270:9849–9855

    Article  PubMed  CAS  Google Scholar 

  399. Jin-Hua P, Goding JW, Nakamura H, Sano K (1997) Molecular cloning and chromosomal localization of PD-Iβ (PDNP3), a new member of the human phosphodiesterase I genes. Genomics 45:412–415

    Article  PubMed  CAS  Google Scholar 

  400. Bello V, Goding JW, Greengrass V, Sali A, Dubljevic V, Lenoir C, Trugnan G, Maurice M (2001) Characterization of a di-leucine-based signal in the cytoplasmic tail of the nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but not endocytosis. Mol Biol Cell 12:3004–3015

    PubMed  CAS  Google Scholar 

  401. Delaunay JL, Breton M, Goding JW, Trugnan G, Maurice M (2007) Differential detergent resistance of the apical and basolateral NPPases: relationship with polarized targeting. J Cell Sci 120:1009–1016

    Article  PubMed  CAS  Google Scholar 

  402. Stracke ML, Krutzsch HC, Unsworth EJ, Arestad AA, Cioce V, Schiffmann E, Liotta LA (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 267:2524–2529

    PubMed  CAS  Google Scholar 

  403. Murata J, Lee HJ, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA, Stracke ML (1994) cDNA cloning of the human motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J Biol Chem 269:30479–30484

    PubMed  CAS  Google Scholar 

  404. Narita M, Goji J, Nakamura H, Sano K (1994) Molecular cloning, expression, and localization of a brain-specific phosphodiesterase I/nucleotide pyrophosphatase (PD-Iα) from rat brain. J Biol Chem 269:28235–28242

    PubMed  CAS  Google Scholar 

  405. Kawagoe H, Soma O, Goji J, Nishimura N, Narita M, Inazawa J, Nakamura H, Sano K (1995) Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2). Genomics 30:380–384

    Article  PubMed  CAS  Google Scholar 

  406. Giganti A, Rodriguez M, Fould B, Moulharat N, Coge F, Chomarat P, Galizzi JP, Valet P, Saulnier-Blache JS, Boutin JA, Ferry G (2008) Murine and human autotaxin α, β, and γ isoforms—gene organization, tissue distribution, and biochemical characterization. J Biol Chem 283:7776–7789

    Article  PubMed  CAS  Google Scholar 

  407. Lee HY, Murata J, Clair T, Polymeropoulos MH, Torres R, Manrow RE, Liotta LA, Stracke ML (1996) Cloning chromosomal localization, and tissue expression of autotaxin from human tetracarcinoma cells. Biochem Biophys Res Commun 218:714–719

    Article  PubMed  CAS  Google Scholar 

  408. Kawagoe H, Stracke ML, Nakamura H, Sano K (1997) Expression and transcriptional regulation of the PD-Iα/autotaxin gene in neuroblastoma. Cancer Res 57:2516–2521

    PubMed  CAS  Google Scholar 

  409. Jansen S, Stefan C, Creemers JWM, Waelkens E, VanEynde A, Stalmans W, Bollen M (2005) Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D. J Cell Sci 118:3081–3089

    Article  PubMed  CAS  Google Scholar 

  410. Koike S, Keino-Masu K, Ohto T, Masu M (2006) The N-terminal hydrophobic sequence of autotaxin (ENPP2) functions as a signal peptide. Genes Cells 11:133–142

    Article  PubMed  CAS  Google Scholar 

  411. Pradere JP, Tarnus E, Gres S, Valet P, Saulnier-Blache JS (2007) Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase. BBA Mol Cell Biol Lipids 1771:93–102

    CAS  Google Scholar 

  412. Gijsbers R, Ceulemans H, Bollen M (2003) Functional characterization of the non-catalytic ectodomains of the nucleotide pyrophosphatase/phosphodiesterase NPP1. Biochem J 371:321–330

    Article  PubMed  CAS  Google Scholar 

  413. Jansen S, Andries M, Derua R, Waelkens E, Bollen M (2009) Domain interplay mediated by an essential disulfide linkage is critical for the activity and secretion of the metastasis-promoting enzyme autotaxin. J Biol Chem 284:14296–14302

    Article  PubMed  CAS  Google Scholar 

  414. Belli SI, Sali A, Goding JW (1994) Divalent cations stabilize the conformation of plasma cell membrane glycoprotein PC-1 (alkaline phosphodiesterase I). Biochem J 304:75–80

    PubMed  CAS  Google Scholar 

  415. Andoh K, JinHua P, Terashima K, Nakamura H, Sano K (1999) Genomic structure and promoter analysis of the ecto-phosphodiesterase I gene (PDNP3) expressed in glial cells. BBA Gene Struct Express 1446:213–224

    Article  CAS  Google Scholar 

  416. Lee J, Jung ID, Nam SW, Clair T, Jeong EM, Hong SY, Han JW, Lee HW, Stracke ML, Lee HY (2001) Enzymatic activation of autotaxin by divalent cations without EF-hand loop region involvement. Biochem Pharmacol 62:219–224

    Article  PubMed  CAS  Google Scholar 

  417. Belli SI, van Driel IR, Goding JW (1993) Identification and characterization of soluble form of the plasma cell membrane glycoprotein PC-1 (5′-nucleotide phosphodiesterase). Eur J Biochem 217:421–428

    Article  PubMed  CAS  Google Scholar 

  418. Stracke ML, Arestad A, Levine M, Krutzsch HC, Liotta LA (1995) Autotaxin is an N-linked glycoprotein but the sugar moieties are not needed for its stimulation of cellular motility. Melanoma Res 5:203–209

    Article  PubMed  CAS  Google Scholar 

  419. Meerson NR, Bello V, Delaunay JL, Slimane TA, Delautier D, Lenoir C, Trugnan G, Maurice M (2000) Intracellular traffic of the ecto-nucleotide pyrophosphatase/phosphodiesterase NPP3 to the epical plasma membrane of MDCK and Caco-2 cells: apical targeting occurs in the absence of N-glycosylation. J Cell Sci 113:4193–4202

    PubMed  CAS  Google Scholar 

  420. Jansen S, Callewaert N, Dewerte I, Andries M, Ceulemans H, Bollen M (2007) An essential oligomannosidic glycan chain in the catalytic domain of autotaxin, a secreted lysophospholipase-D. J Biol Chem 282:11084–11091

    Article  PubMed  CAS  Google Scholar 

  421. Ohe Y, Ohnishi H, Okazawa H, Tomizawa K, Kobayashi H, Okawa K, Matozaki T (2003) Characterization of nucleotide pyrophosphatase-5 as an oligomannosidic glycoprotein in rat brain. Biochem Biophys Res Commun 308:719–725

    Article  PubMed  CAS  Google Scholar 

  422. Meerson NR, Delautier D, Durand-Schneider AM, Moreau A, Schilsky ML, Sternlieb I, Feldmann G, Maurice M (1998) Identification of B10, an alkaline phosphodiesterase of the apical plasma membrane of hepatocytes and biliary cells, in rat serum: increased levels following bile duct ligation and during the development of cholangiocarcinoma. Hepatology 27:563–568

    Article  PubMed  CAS  Google Scholar 

  423. Wu J, Liu F, Nilsson A, Duan RD (2004) Pancreatic trypsin cleaves intestinal alkaline sphingomyelinase from mucosa and enhances the sphingomyelinase activity. Am J Physiol Gastrointest Liver Physiol 287:G967–G973

    Article  PubMed  CAS  Google Scholar 

  424. Yegutkin GG, Samburski SS, Jalkanen S (2003) Soluble purine-converting enzymes circulate in human blood and regulate extracellular ATP level via counteracting pyrophosphatase and phosphotransfer reactions. FASEB J 17:U15–U34

    Google Scholar 

  425. Laketa D, Bjelobaba I, Savic J, Lavrnja I, Stojiljkovic M, Rakic L, Nedeljkovic N (2010) Biochemical characterization of soluble nucleotide pyrophosphatase/phosphodiesterase activity in rat serum. Mol Cell Biochem 339:99–106

    Article  PubMed  CAS  Google Scholar 

  426. Nakabayashi T, Ikezawa H (1986) Alkaline phosphodiesterase I release from eucaryotic plasma membranes by phophatidylinositol-specific phospholipase C. I. The release from rat organs. J Biochem 99:703–712

    PubMed  CAS  Google Scholar 

  427. Nakabayashi T, Ikezawa H (1986) Alkaline phosphodiesterase I release from eucaryotic plasma membranes by phosphatidylinositol-specific phospholipase C. II. The release from brush border membranes of porcine intestine. Toxicon 24:975–984

    Article  PubMed  CAS  Google Scholar 

  428. Nakabayashi T, Matsuoka Y, Ikezawa H, Kimura Y (1994) Alkaline phosphodiesterase I release from eucaryotic plasma membranes by phosphatidylinositol-specific phospholipase C—IV. The release from Cacia porcellus organs. Int J Biochem 26:171–179

    Article  PubMed  CAS  Google Scholar 

  429. Itami C, Taguchi R, Ikezawa H, Nakabayashi T (1997) Release of ectoenzymes from small intestine brush border membranes of mice by phospholipases. Biosci Biotechnol Biochem 61:336–340

    Article  PubMed  CAS  Google Scholar 

  430. Pamuklar Z, Federico L, Liu SY, Umezu-Goto M, Dong AP, Panchatcharam M, Fulerson Z, Berdyshev E, Natarajan V, Fang XJ, van Meeteren LA, Moolenaar WH, Mills GB, Morris AJ, Smyth SS (2009) Autotaxin/lysopholipase D and lysophosphatidic acid regulate murine hemostasis and thrombosis. J Biol Chem 284:7385–7394

    Article  PubMed  CAS  Google Scholar 

  431. Hausmann J, Kamtekar S, Christodoulou E, Day JE, Wu T, Fulkerson Z, Albers HM, van Meeteren LA, Houben AJ, van Zeijl L, Jansen S, Andries M, Hall T, Pegg LE, Benson TE, Kasiem M, Harlos K, Kooi CW, Smyth SS, Ovaa H, Bollen M, Morris AJ, Moolenaar WH, Perrakis A (2011) Structural basis of substrate discrimination and integrin binding by autotaxin. Nat Struct Mol Biol 18:198–U262

    Article  PubMed  CAS  Google Scholar 

  432. Fox MA, Colello RJ, Macklin WB, Fuss B (2003) Phosphodiesterase-I α/autotaxin: a counteradhesive protein expressed by oligodendrocytes during onset of myelination. Mol Cell Neurosci 23:507–519

    Article  PubMed  CAS  Google Scholar 

  433. Fox MA, Alexander JK, Afshari FS, Colello RJ, Fuss B (2004) Phosphodieterase-I α/autotaxin and IFAK phosphorylation during controls cytoskeletal organization myelination. Mol Cell Neurosci 27:140–150

    Article  PubMed  CAS  Google Scholar 

  434. Dennis J, White MA, Forrest AD, Yuelling LM, Nogaroli L, Afshari FS, Fox MA, Fuss B (2008) Phosphodiesterase-I alpha/autotaxin’s MORFO domain regulates oligodendroglial process network formation and focal adhesion organization. Mol Cell Neurosci 37:412–424

    Article  PubMed  CAS  Google Scholar 

  435. Grobben B, Claes P, Roymans D, Esmans EL, van Onckelen H, Slegers H (2000) Ecto-nucleotide pyrophosphatase modulates the purinoceptor-mediated signal transduction and is inhibited by purinoceptor antagonists. Brit J Pharmacol 130:139–145

    Article  CAS  Google Scholar 

  436. Delicado EG, Miras-Portugal MT, Carrasquero LMG, León D, Pérez-Sen R, Gualix J (2006) Dinucleoside polyphosphates and their interaction with other nucleotide signaling pathways. Pflugers Arch Eur J Physiol 452:563–572

    Article  CAS  Google Scholar 

  437. Hoyle CHV, Hilderman RH, Pintor JJ, Schlüter H, King BF (2001) Diadenosine polyphosphates as extracellular signal molecules. Drug Develop Res 52:260–273

    Article  CAS  Google Scholar 

  438. Massé K, Bhamra S, Allsop G, Dale N, Jones EA (2010) Ectophosphodiesterase/nucleotide phosphohydrolase (Enpp) nucleotidases: cloning, conservation and developmental restriction. Int J Dev Biol 54:181–193

    Article  PubMed  CAS  Google Scholar 

  439. Nakanaga K, Hama K, Aoki J (2010) Autotaxin—an LPA producing enzyme with diverse functions. J Biochem 148:13–24

    Article  PubMed  CAS  Google Scholar 

  440. Laidlaw SM, Anwar MA, Thomas W, Green P, Shaw K, Skinner MA (1998) Fowlpox virus encodes nonessential homologs of cellular alpha-SNAP, PC-1, and an orphan human homolog of a secreted nematode protein. J Virol 72:6742–6751

    PubMed  CAS  Google Scholar 

  441. Zalatan JG, Fenn TD, Brunger AT, Herschlag D (2006) Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution. Biochemistry USA 45:9788–9803

    Article  CAS  Google Scholar 

  442. Zalatan JG, Fenn TD, Herschlag D (2008) Comparative enzymology in the alkaline phosphatase superfamily to determine the catalytic role of an active-site metal ion. J Mol Biol 384:1174–1189

    Article  PubMed  CAS  Google Scholar 

  443. Galperin MY, Bairoch A, Koonin EV (1998) A superfamily of metalloenzymes unifies phosphopentomutase and cofactor-independent phosphoglycerate mutase with alkaline phosphatases and sulfatases. Protein Sci 7:1829–1835

    Article  PubMed  CAS  Google Scholar 

  444. Galperin MY, Jedrzejas MJ (2001) Conserved core structure and active site residues in alkaline phosphatase superfamily enzymes. Protein Struct Funct Genet 45:318–324

    Article  CAS  Google Scholar 

  445. Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O (2011) Crystal structure of autotaxin and insight into GPCR activation by lipid mediators. Nat Struct Mol Biol 18:205–U271

    Article  PubMed  CAS  Google Scholar 

  446. Le Du MH, Stigbrand T, Taussig MJ, Menez A, Stura EA (2001) Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution—implication for a substrate specificity. J Biol Chem 276:9158–9165

    Article  PubMed  Google Scholar 

  447. Hoylaerts MF, Ding L, Narisawa S, Van Kerckhoven S, Millán JL (2006) Mammalian alkaline phosphatase catalysis requires active site structure stabilization via the N-terminal amino acid microenvironment. Biochemistry USA 45:9756–9766

    Article  CAS  Google Scholar 

  448. Kim A, Benning MM, OkLee S, Quinn J, Martin BM, Holden HM, Dunaway-Mariano D (2011) Divergence of chemical function in the alkaline phosphatase superfamily: structure and mechanism of the P-C bond cleaving enzyme phosphonoacetate hydrolases. Biochemistry USA 50:3481–3494

    Article  CAS  Google Scholar 

  449. Inoue K, Tanaka N, Haga A, Yamasaki K, Umeda T, Kusakabe Y, Sakamoto Y, Nonaka T, Deyashiki Y, Nakamura KT (2011) Crystallization and preliminary X-ray crystallographic analysis of human autotaxin. Acta Crystallogr Sect F Struct Biol Cryst Commun 67:450–453

    Article  PubMed  CAS  Google Scholar 

  450. Kamikubo Y, De GR, Kroon G, Curriden S, Neels JG, Churchill MJ, Dawson P, Oldziej S, Jagielska A, Scheraga HA, Loskutoff DJ, Dyson HJ (2004) Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin. Biochemistry USA 43:6519–6534

    Article  CAS  Google Scholar 

  451. Kanda H, Newton R, Klein R, Morita Y, Gunn MD, Rosen SD (2008) Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs. Nat Immunol 9:415–423

    Article  PubMed  CAS  Google Scholar 

  452. Culp JS, Blytt HJ, Hermodson M, Butler LG (1985) Amino acid sequence of the active site peptide of bovine intestinal 5′-nucleotide phosphodiesterase and identification of the active site residue as threonine. J Biol Chem 260:8320–8324

    PubMed  CAS  Google Scholar 

  453. Stefan C, Stalmans W, Bollen M (1996) Threonine autophosphorylation and nucleotidylation of the hepatic membrane protein PC-1. Eur J Biochem 241:338–342

    Article  PubMed  CAS  Google Scholar 

  454. Joye IJ, Belien T, Brijs K, Soetaert W, Delcour JA (2011) Mutational analysis of wheat (Triticum aestivum L.) nucleotide pyrophosphatase/phosphodiesterase shows the role of six amino acids in the catalytic mechanism. Appl Microbiol Biotechnol 90:173–180

    Article  PubMed  CAS  Google Scholar 

  455. Eichholz A, Crane RK (1974) Isolation of plasma membranes from intestinal brush borders. Methods Enzymol 31:123–134

    Article  PubMed  CAS  Google Scholar 

  456. Giocondi MC, Seantier B, Dosset P, Milhiet PE, Le GC (2008) Characterizing the interactions between GPI-anchored alkaline phosphatases and membrane domains by AFM. Pflugers Arch 456:179–188

    Article  PubMed  CAS  Google Scholar 

  457. Gouridis G, Karamanou S, Koukaki M, Economou A (2010) In vitro assays to analyze translocation of the model secretory preprotein alkaline phosphatase. Methods Mol Biol 619:157–172

    Article  PubMed  CAS  Google Scholar 

  458. Coleman JE (1992) Structure and mechanism of alkaline phosphatase. Ann Rev Biophys Biomol Struct 21:441–483

    Article  CAS  Google Scholar 

  459. McComb RB, Bowers GN, Posen S (1979) Alkaline phosphatase. Plenum, New York

    Book  Google Scholar 

  460. Millán JL (1992) Alkaline phosphatase as a reporter of cancerous transformation. Clin Chim Acta 209:123–129

    Article  PubMed  Google Scholar 

  461. Epstein E, Kiechle FL, Artiss JD, Zak B (1986) The clinical use of alkaline phosphatase enzymes. Clin Lab Med 6:491–505

    PubMed  CAS  Google Scholar 

  462. Shirley DG, Vekaria RM, Sévigny J (2009) Ectonucleotidases in the kidney. Purinergic Signal 5:501–511

    Article  PubMed  CAS  Google Scholar 

  463. Lynes MD, Widmaier EP (2011) Involvement of CD36 and intestinal alkaline phosphatases in fatty acid transport in enterocytes, and the response to a high-fat diet. Life Sci 88:384–391

    Article  PubMed  CAS  Google Scholar 

  464. Picher M, Burch LH, Hirsh AJ, Spychala J, Boucher RC (2003) Ecto-5′-nucleotidase and nonspecific alkaline phosphatase—two AMP-hydrolyzing ectoenzymes with distinct roles in human airways. J Biol Chem 278:13468–13479

    Article  PubMed  CAS  Google Scholar 

  465. Pease S, Braghetta P, Gearing D, Grail D, Williams RL (1990) Isolation of embryonic stem (ES) cells in media supplemented with recombinant leukemia inhibitory factor (LIF). Dev Biol 141:344–352

    Article  PubMed  CAS  Google Scholar 

  466. Heath JK (1978) Characterization of a xenogeneic antiserum raised against the fetal germ cells of the mouse: cross-reactivity with embryonal carcinoma cells. Cell 15:299–306

    Article  PubMed  CAS  Google Scholar 

  467. Langer D, Ikehara Y, Takebayashi H, Hawkes R, Zimmermann H (2007) The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones. Neuroscience 150:863–879

    Article  PubMed  CAS  Google Scholar 

  468. Fonta C, Negyessy L, Renaud L, Barone P (2005) Postnatal development of alkaline phosphatase activity correlates with the maturation of neurotransmission in the cerebral cortex. J Comp Neurol 486:179–196

    Article  PubMed  Google Scholar 

  469. Negyessy L, Xiao J, Kantor O, Kovacs GG, Palkovits M, Doczi TP, Renaud L, Baksa G, Glasz T, Ashaber M, Barone P, Fonta C (2011) Layer-specific activity of tissue non-specific alkaline phosphatase in the human neocortex. Neuroscience 172:406–418

    Article  PubMed  CAS  Google Scholar 

  470. Iida M, Ihara S, Matsuzaki T (2007) Hair cycle-dependent changes of alkaline phosphatase activity in the mesenchyme and epithelium in mouse vibrissal follicles. Develop Growth Differ 49:185–195

    Article  CAS  Google Scholar 

  471. Aldag I, Bockau U, Rossdorf J, Laarmann S, Raaben W, Herrmann L, Weide T, Hartmann MW (2011) Expression, secretion and surface display of a human alkaline phosphatase by the ciliate Tetrahymena thermophila. BMC Biotechnol 11:11

    Article  PubMed  CAS  Google Scholar 

  472. Narisawa S, Hoylaerts MF, Doctor KS, Fukuda MN, Alpers DH, Millán JL (2007) A novel phosphatase upregulated in Akp3 knockout mice. Amer J Physiol Gastrointest L 293:G1068–G1077

    Article  CAS  Google Scholar 

  473. Millán JL (2006) Mammalian alkaline phosphatase. From biology to applications in medicine and biotechnology. Wiley, Weinheim

    Book  Google Scholar 

  474. Millán JL (2006) Alkaline phosphatases: structure, substrate specificity and functional relatedness to other members of a large superfamily of enzymes. Purinergic Signal 2:335–341

    Article  PubMed  CAS  Google Scholar 

  475. Le Du MH, Millán JL (2002) Structural evidence of functional divergence in human alkaline phosphatases. J Biol Chem 277:49808–49814

    Article  PubMed  Google Scholar 

  476. Hoylaerts MF, Manes T, Millán JL (1997) Mammalian alkaline phosphatases are allosteric enzymes. J Biol Chem 272:22781–22787

    Article  PubMed  CAS  Google Scholar 

  477. Saslowsky DE, Lawrence J, Ren XY, Brown DA, Henderson RM, Edwardson JM (2002) Placental alkaline phosphatase is efficiently targeted to rafts in supported lipid bilayers. J Biol Chem 277:26966–26970

    Article  PubMed  CAS  Google Scholar 

  478. Suzuki T, Ishihara K, Migaki H, Matsuura W, Kohda A, Okumura K, Nagao M, Yamaguchi-Iwai Y, Kambe T (2005) Zinc transporters, ZnT5 and ZnT7, are required for the activation of alkaline phosphatases, zinc-requiring enzymes that are glycosylphosphatidylinositol-anchored to the cytoplasmic membrane. J Biol Chem 280:637–643

    PubMed  CAS  Google Scholar 

  479. Suzuki T, Ishihara K, Migaki H, Ishihara K, Nagao M, Yamaguchi-Iwai Y, Kambe T (2005) Two different zinc transport complexes of cation diffusion facilitator proteins localized in the secretory pathway operate to activate alkaline phosphatases in vertebrate cells. J Biol Chem 280:30956–30962

    Article  PubMed  CAS  Google Scholar 

  480. Fukunaka A, Kurokawa Y, Teranishi F, Sekler I, Oda K, Ackland ML, Faundez V, Hiromura M, Masuda S, Nagao M, Enomoto S, Kambe T (2011) Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. J Biol Chem 286:16363–16373

    Article  PubMed  CAS  Google Scholar 

  481. Ishihara K, Yamazaki T, Ishida Y, Suzuki T, Oda K, Nagao M, Yamaguchi-Iwai Y, Kambe T (2006) Zinc transport complexes contribute to the homeostatic maintenance of secretory pathway function in vertebrate cells. J Biol Chem 281:17743–17750

    Article  PubMed  CAS  Google Scholar 

  482. O'Brien PJ, Herschlag D (2001) Functional interrelationships in the alkaline phosphatase superfamily: phosphodiesterase activity of Escherichia coli alkaline phosphatase. Biochemistry USA 40:5691–5699

    Article  CAS  Google Scholar 

  483. Rezende AA, Pizauro JM, Ciancaglini P, Leone FA (1994) Phosphodiesterase activity is a novel property of alkaline phosphatase from osseous plate. Biochem J 301:517–522

    PubMed  CAS  Google Scholar 

  484. Jiang T, Xing B, Rao J (2008) Recent developments of biological reporter technology for detecting gene expression. Biotechnol Genet Eng Rev 25:41–75

    Article  PubMed  CAS  Google Scholar 

  485. Whyte PP (1996) Hypophosphatasia: natures window on alkaline phosphatase function in man. In: Bilezkian J, Raisz L, Rodan G (eds) Principles of bone biology. Academic, San Diego, pp 951–968

    Google Scholar 

  486. Mornet E (2007) Hypophosphatasia. Orphanet J Rare Dis 2:40

    Article  PubMed  Google Scholar 

  487. Whyte MP (2010) Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci 1192:190–200

    Article  PubMed  CAS  Google Scholar 

  488. MacGregor GR, Zambrowicz BP, Soriano P (1995) Tissue non-specific alkaline phosphatase is expressed in both embryonic and extraembryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. Development 121:1487–1496

    PubMed  CAS  Google Scholar 

  489. Waymire JC, Mahuren JD, Jaje JM, Guilarte T, Coburn SP, MacGregor GR (1995) Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nature Genet 11:45–51

    Article  PubMed  CAS  Google Scholar 

  490. Narisawa S, Fröhlander N, Millán JL (1997) Inactivation of two mouse alkaline phosphatase genes and establishment of a model of infantile hypophosphatasia. Develop Dynam 208:432–446

    Article  CAS  Google Scholar 

  491. Anderson HC, Sipe JB, Hessle L, Dhamyamraju R, Atti E, Camacho NP, Millán JL (2004) Impaired calcification around matrix vesicles of growth plate and bone in alkaline phosphatase-deficient mice. Amer J Pathol 164:841–847

    Article  CAS  Google Scholar 

  492. Fedde KN, Blair L, Silverstein J, Coburn SP, Ryan LM, Weinstein RS, Waymire K, Narisawa S, Millán JL, MacGregor GR, Whyte MP (1999) Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 14:2015–2026

    Article  PubMed  CAS  Google Scholar 

  493. Millán JL, Narisawa S, Lemire I, Loisel TP, Boileau G, Leonard P, Gramatikova S, Terkeltaub R, Camacho NP, Mckee MD, Crine P, Whyte MP (2008) Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res 23:777–787

    Article  PubMed  Google Scholar 

  494. Yadav MC, Lemire I, Leonard P, Boileau G, Blond L, Beliveau M, Cory E, Sah RL, Whyte MP, Crine P, Millán JL (2011) Dose response of bone-targeted enzyme replacement for murine hypophosphatasia. Bone 49:250–256

    Article  PubMed  CAS  Google Scholar 

  495. Yamamoto S, Orimo H, Matsumoto T, Iijima O, Narisawa S, Maeda T, Millán JL, Shimada T (2011) Prolonged survival and phenotypic correction of Akp2(−/−) hypophosphatasia mice by lentiviral gene therapy. J Bone Miner Res 26:135–142

    Article  PubMed  CAS  Google Scholar 

  496. Smith GP, Peters TJ (1981) Subcellular localization and properties of pyridoxal phosphate phosphatases of human polymorphonuclear leukocytes and their relationship to acid and alkaline phosphatase. Biochim Biophys Acta 661:287–294

    PubMed  CAS  Google Scholar 

  497. Wilson PD, Smith GP, Peters TJ (1983) Pyridoxal 5′-phosphate: a possible physiological substrate for alkaline phosphatase in human neutrophils. Histochem J 15:257–264

    Article  PubMed  CAS  Google Scholar 

  498. Whyte MP, Landt M, Ryan LM, Mulivor RA, Henthorn PS, Fedde KN, Mahuren JD, Coburn SP (1995) Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5′-phosphate—substrate accumulation in carriers of hypophosphatasia corrects during pregnancy. J Clin Invest 95:1440–1445

    Article  PubMed  CAS  Google Scholar 

  499. Narisawa S, Wennberg C, Millán JL (2001) Abnormal vitamin B6 metabolism in alkaline phosphatase knock-out mice causes multiple abnormalities, but not the impaired bone mineralization. J Pathol 193:125–133

    Article  PubMed  CAS  Google Scholar 

  500. Poelstra K, Bakker WW, Klok PA, Kamps JA, Hardonk MJ, Meijer DK (1997) Dephosphorylation of endotoxin by alkaline phosphatase in vivo. Am J Pathol 151:1163–1169

    PubMed  CAS  Google Scholar 

  501. Bates JM, Akerlund J, Mittge E, Guillemin K (2007) Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe 2:371–382

    Article  PubMed  CAS  Google Scholar 

  502. Geddes K, Philpott DJ (2008) A new role for intestinal alkaline phosphatase in gut barrier maintenance. Gastroenterology 135:8–12

    Article  PubMed  CAS  Google Scholar 

  503. Goldberg RF, Austen WG Jr, Zhang X, Munene G, Mostafa G, Biswas S, McCormack M, Eberlin KR, Nguyen JT, Tatlidede HS, Warren HS, Narisawa S, Millán JL, Hodin RA (2008) Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci USA 105:3551–3556

    Article  PubMed  CAS  Google Scholar 

  504. Lalles JP (2010) Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr Rev 68:323–332

    Article  PubMed  Google Scholar 

  505. Malo MS, Alam SN, Mostafa G, Zeller SJ, Johnson PV, Mohammad N, Chen KT, Moss AK, Ramasamy S, Faruqui A, Hodin S, Malo PS, Ebrahimi F, Biswas B, Narisawa S, Millán JL, Warren HS, Kaplan JB, Kitts CL, Hohmann EL, Hodin RA (2010) Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota. Gut 59:1476–1484

    Article  PubMed  CAS  Google Scholar 

  506. Chen KT, Malo MS, Beasley-Topliffe LK, Poelstra K, Millán JL, Mostafa G, Alam SN, Ramasamy S, Warren HS, Hohmann EL, Hodin RA (2011) A role for intestinal alkaline phosphatase in the maintenance of local gut immunity. Dig Dis Sci 56:1020–1027

    Article  PubMed  CAS  Google Scholar 

  507. Tuin A, Huizinga-Van der Vlag A, van Loenen-Weemaes AM, Meijer DK, Poelstra K (2006) On the role and fate of LPS-dephosphorylating activity in the rat liver. Am J Physiol Gastrointest Liver Physiol 290:G377–G385

    Article  PubMed  CAS  Google Scholar 

  508. Swarup G, Cohen S, Garbers DL (1981) Selective dephosphorylation of proteins containing phosphotyrosine by alkaline phosphatases. J Biol Chem 256:8197–8201

    PubMed  CAS  Google Scholar 

  509. Bütikofer P, Vassella E, Ruepp S, Boschung M, Civenni G, Seebeck T, Hemphill A, Mookherjee N, Pearson TW, Roditi I (1999) Phosphorylation of a major GPI-anchored surface protein of Trypanosoma brucei during transport to the plasma membrane. J Cell Sci 112:1785–1795

    PubMed  Google Scholar 

  510. Scheibe RJ, Kuehl H, Krautwald S, Meissner JD, Mueller WH (2000) Ecto-alkaline phosphatase activity identified at physiological pH range on intact P19 and HL-60 cells is induced by retinoic acid. J Cell Biochem 76:420–436

    Article  PubMed  CAS  Google Scholar 

  511. Ermonval M, Baudry A, Baychelier F, Pradines E, Pietri M, Oda K, Schneider B, Mouillet-Richard S, Launay JM, Kellermann O (2009) The cellular prion protein interacts with the tissue non-specific alkaline phosphatase in membrane microdomains of bioaminergic neuronal cells. PLoS One 4:e6497

    Article  PubMed  CAS  Google Scholar 

  512. Kanshin E, Wang S, Ashmarina L, Fedjaev M, Nifant'ev I, Mitchell GA, Pshezhetsky AV (2009) The stoichiometry of protein phosphorylation in adipocyte lipid droplets: analysis by N-terminal isotope tagging and enzymatic dephosphorylation. Proteomics 9:5067–5077

    Article  PubMed  CAS  Google Scholar 

  513. Díaz-Hernández M, Gómez-Ramos A, Rubio A, Gómez-Villafuertes R, Naranjo JR, Miras-Portugal MT, Avila J (2010) Tissue-nonspecific alkaline phosphatase promotes the neurotoxicity effect of extracellular tau. J Biol Chem 285:32539–32548

    Article  PubMed  CAS  Google Scholar 

  514. Say JC, Ciuffi K, Furriel RP, Ciancaglini P, Leone FA (1991) Alkaline phosphatase from rat osseous plates: purification and biochemical characterization of a soluble form. Biochim Biophys Acta 1074:256–262

    Article  PubMed  CAS  Google Scholar 

  515. Ohkubo S, Kimura J, Matsuoka I (2000) Ecto-alkaline phosphatase in NG108-15 cells: a key enzyme mediating P1 antagonist-sensitive ATP response. Brit J Pharmacol 131:1667–1672

    Article  CAS  Google Scholar 

  516. Picher M, Burch LH, Boucher RC (2004) Metabolism of P2 receptor agonists in human airways—implications for mucociliary clearance and cystic fibrosis. J Biol Chem 279:20234–20241

    Article  PubMed  CAS  Google Scholar 

  517. Díez-Zaera M, Díaz-Hernández JI, Hernández-Álvarez E, Zimmermann H, Díaz-Hernández M, Miras-Portugal MT (2011) Tissue-nonspecific alkaline phosphatase promotes axonal growth of hippocampal neurons. Mol Biol Cell 22:1014–1024

    Article  PubMed  CAS  Google Scholar 

  518. Pizauro JM, Demenis MA, Ciancaglini P, Leone FA (1998) Kinetic characterization of a membrane-specific ATPase from rat osseous plate and its possible significance on endochodral ossification. Biochim Biophys Acta 1368:108–114

    Article  PubMed  CAS  Google Scholar 

  519. Pizauro JM, Ciancaglini P, Leone FA (1993) Allosteric modulation by ATP, calcium and magnesium ions of rat osseous plate alkaline phosphatase. Biochim Biophys Acta 1202:22–28

    Article  PubMed  CAS  Google Scholar 

  520. Demenis MA, Leone FA (2000) Kinetic characteristics of ATP hydrolysis by a detergent-solubilized alkaline phosphatase from rat osseous plate. IUBMB Life 49:113–119

    Article  PubMed  CAS  Google Scholar 

  521. Simão AMS, Beloti MM, Cezarino RM, Rosa AL, Pizauro JM, Ciancaglini P (2007) Membrane-bound alkaline phosphatase from ectopic mineralization and rat bone marrow cell culture. Comp Biochem Physiol Pt A 146:679–687

    Article  CAS  Google Scholar 

  522. Kam W, Clauser EM, Kim YS, Kan YW, Rutter WJ (1985) Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA. Proc Natl Acad Sci USA 82:8715–8719

    Article  PubMed  CAS  Google Scholar 

  523. Millán JL (1986) Molecular cloning and sequence analysis of human placental alkaline phosphatase. J Biol Chem 261:3112–3115

    PubMed  Google Scholar 

  524. Henthorn PS, Knoll BJ, Raducha M, Rothblum KN, Slaughter C, Weiss M, Lafferty MA, Fischer T, Harris H (1986) Products of two common alleles at the locus for human placental alkaline phosphatase differ by seven amino acids. Proc Natl Acad Sci USA 83:5597–5601

    Article  PubMed  CAS  Google Scholar 

  525. Berger J, Garattini E, Hua JC, Udenfriend S (1987) Cloning and sequencing of human intestinal alkaline phosphatase cDNA. Proc Natl Acad Sci USA 84:695–698

    Article  PubMed  CAS  Google Scholar 

  526. Henthorn PS, Raducha M, Edwards YH, Weiss MJ, Slaughter C, Lafferty MA, Harris H (1987) Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase. Proc Natl Acad Sci USA 84:1234–1238

    Article  PubMed  CAS  Google Scholar 

  527. Weiss MJ, Henthorn PS, Lafferty MA, Slaughter C, Raducha M, Harris H (1986) Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase. Proc Natl Acad Sci USA 83:7182–7186

    Article  PubMed  CAS  Google Scholar 

  528. Terao M, Mintz B (1987) Cloning and characterization of a cDNA coding for mouse placental alkaline phosphatase. Proc Natl Acad Sci USA 84:7051–7055

    Article  PubMed  CAS  Google Scholar 

  529. Knoll BJ, Rothblum KN, Longley M (1987) Two gene duplication events in the evolution of the human heat-stable alkaline phosphatases. Gene 60:267–276

    Article  PubMed  CAS  Google Scholar 

  530. Millán JL, Manes T (1988) Seminoma-derived Nagao isozyme is encoded by a germ-cell alkaline phosphatase gene. Proc Natl Acad Sci USA 85:3024–3028

    Article  PubMed  Google Scholar 

  531. Fishman WH (1990) Alkaline phosphatase isozymes: recent progress. Clin Biochem 23:99–104

    Article  PubMed  CAS  Google Scholar 

  532. Kozlenkov A, Manes T, Hoylaerts MF, Millán JL (2002) Function assignment to conserved residues in mammalian alkaline phosphatases. J Biol Chem 277:22992–22999

    Article  PubMed  CAS  Google Scholar 

  533. Kishi F, Matsuura S, Kajii T (1989) Nucleotide sequence of the human liver-type alkaline phosphatase cDNA. Nucleic Acids Res 17:2129

    Article  PubMed  CAS  Google Scholar 

  534. Toh Y, Yamamoto M, Endo H, Fujita A, Misumi Y, Ikehara Y (1989) Sequence divergence of 5′ extremities in rat liver alkaline phosphatase mRNAs. J Biochem 105:61–65

    PubMed  CAS  Google Scholar 

  535. Toh Y, Yamamoto M, Endo H, Misumi Y, Ikehara Y (1989) Isolation and characterization of a rat liver alkaline phosphatase gene. A single gene with two promoters. Eur J Biochem 182:231–237

    Article  PubMed  CAS  Google Scholar 

  536. Zernik J, Kream B, Twarog K (1991) Tissue-specific and dexamethasone-inducible expression of alkaline phosphatase from alternative promoters of the rat bone/liver/kidney/placenta gene. Biochem Biophys Res Commun 176:1149–1156

    Article  PubMed  CAS  Google Scholar 

  537. Studer M, Terao M, Gianni M, Garattini E (1991) Characterization of a second promoter for the mouse liver/bone/kidney-type alkaline phosphatase gene: cell and tissue specific expression. Biochem Biophys Res Commun 179:1352–1360

    Article  PubMed  CAS  Google Scholar 

  538. Nosjean O, Koyama I, Goseki M, Roux B, Komoda T (1997) Human tissue non-specific alkaline phosphatases: sugar-moiety-induced enzymic and antigenic modulations and genetic aspects. Biochem J 321(Pt 2):297–303

    PubMed  CAS  Google Scholar 

  539. Kuwana T, Sugita O, Yakata M (1991) Sugar chain heterogeneity of bone and liver alkaline phosphatase in serum. Enzyme 45:63–66

    PubMed  CAS  Google Scholar 

  540. Garattini E, Hua JC, Pan YC, Udenfriend S (1986) Human liver alkaline phosphatase, purification and partial sequencing: homology with the placental isozyme. Arch Biochem Biophys 245:331–337

    Article  PubMed  CAS  Google Scholar 

  541. Farley JR, Magnusson P (2005) Effects of tunicamycin, mannosamine, and other inhibitors of glycoprotein processing on skeletal alkaline phosphatase in human osteoblast-like cells. Calcified Tissue Int 76:63–74

    Article  CAS  Google Scholar 

  542. Pan CJ, Sartwell AD, Chou JY (1991) Transcriptional regulation and the effects of sodium butyrate and glycosylation on catalytic activity of human germ cell alkaline phosphatase. Cancer Res 51:2058–2062

    PubMed  CAS  Google Scholar 

  543. Mueller WH, Kleefeld D, Khattab B, Meissner JD, Scheibe RJ (2000) Effects of retinoic acid on N-glycosylation and mRNA stability of the liver/bone/kidney alkaline phosphatase in neuronal cells. J Cell Physiol 182:50–61

    Article  PubMed  CAS  Google Scholar 

  544. Linder CH, Narisawa S, Millán JL, Magnusson P (2009) Glycosylation differences contribute to distinct catalytic properties among bone alkaline phosphatase isoforms. Bone 45:987–993

    Article  CAS  Google Scholar 

  545. Magnusson P, Farley JR (2002) Differences in sialic acid residues among bone alkaline phosphatase isoforms: a physical, biochemical, and immunological characterization. Calcified Tissue Int 71:508–518

    Article  CAS  Google Scholar 

  546. Endo T, Ohbayashi H, Hayashi Y, Ikehara Y, Kochibe N, Kobata A (1988) Structural study on the carbohydrate moiety of human placental alkaline phosphatase. J Biochem 103:182–187

    PubMed  CAS  Google Scholar 

  547. Nam JH, Zhang F, Ermonval M, Linhardt RJ, Sharfstein ST (2008) The effects of culture conditions on the glycosylation of secreted human placental alkaline phosphatase produced in Chinese hamster ovary cells. Biotechnol Bioeng 100:1178–1192

    Article  PubMed  CAS  Google Scholar 

  548. Catino MA, Paladino S, Tivodar S, Pocard T, Zurzolo C (2008) N- and O-glycans are not directly involved in the oligomerization and apical sorting of GPI proteins. Traffic 9:2141–2150

    Article  PubMed  CAS  Google Scholar 

  549. Endo T, Higashino K, Hada T, Imanishi H, Muratani K, Kochibe N, Kobata A (1990) Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. Cancer Res 50:1079–1084

    PubMed  CAS  Google Scholar 

  550. Slein MW, Logan GF (1965) Characterization of the phospholipases of Bacillus cereus and their effects on erythrocytes, bone, and kidney cells. J Bacteriol 90:69–81

    PubMed  CAS  Google Scholar 

  551. Ikezawa H, Yamanegi M, Taguchi R, Miyashita T, Ohyabu T (1976) Studies on phosphatidylinositol phosphodiesterase (phospholipase C type) of Bacillus cereus. I. Purification, properties and phosphatase-releasing activity. Biochim Biophys Acta 450:154–164

    PubMed  CAS  Google Scholar 

  552. Low MG, Finean JB (1977) Release of alkaline phosphatase from membranes by a phosphatidylinositol-specific phospholipase C. Biochem J 167:281–284

    PubMed  CAS  Google Scholar 

  553. Wong YW, Low MG (1992) Phospholipase resistance of the glycosyl-phosphatidylinositol membrane anchor on human alkaline phosphatase. Clin Chem 38:2517–2525

    PubMed  CAS  Google Scholar 

  554. Wong YW, Low MG (1994) Biosynthesis of glycosylphosphatidylinositol-anchored human placental alkaline phosphatase: evidence for a phospholipase C-sensitive precursor and its post-attachment conversion into a phospholipase C-resistant form. Biochem J 301:205–209

    PubMed  CAS  Google Scholar 

  555. Micanovic R, Gerber LD, Berger J, Kodukula K, Udenfriend S (1990) Selectivity of the cleavage/attachment site of phosphatidylinositol-glycan-anchored membrane proteins determined by site-specific mutagenesis at Asp-484 of placental alkaline phosphatase. Proc Natl Acad Sci USA 87:157–161

    Article  PubMed  CAS  Google Scholar 

  556. Ogata S, Hayashi Y, Takami N, Ikehara Y (1988) Chemical characterization of the membrane-anchoring domain of human placental alkaline phosphatase. J Biol Chem 263:10489–10494

    PubMed  CAS  Google Scholar 

  557. Lowe ME (1992) Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein. J Cell Biol 116:799–807

    Article  PubMed  CAS  Google Scholar 

  558. Bailey CA, Gerber L, Howard AD, Udenfriend S (1989) Processing at the carboxyl terminus of nascent placental alkaline phosphatase in a cell-free system: evidence for specific cleavage of a signal peptide. Proc Natl Acad Sci USA 86:22–26

    Article  PubMed  CAS  Google Scholar 

  559. Amthauer R, Kodukula K, Udenfriend S (1992) Placental alkaline phosphatase: a model for studying COOH-terminal processing of phosphatidylinositol-glycan-anchored membrane proteins. Clin Chem 38:2510–2516

    PubMed  CAS  Google Scholar 

  560. Redman CA, Thomas-Oates JE, Ogata S, Ikehara Y, Ferguson MAJ (1994) Structure of the glycosylphosphatidylinositol membrane anchor of human placental alkaline phosphatase. Biochem J 302:861–865

    PubMed  CAS  Google Scholar 

  561. Fukushima K, Ikehara Y, Kanai M, Kochibe N, Kuroki M, Yamashita K (2003) A β-N-acetylglucosaminyl phosphate diester residue is attached to the glycosylphosphatidylinositol anchor of human placental alkaline phosphatase—a target of the channel-forming toxin aerolysin. J Biol Chem 278:36296–36303

    Article  PubMed  CAS  Google Scholar 

  562. Giocondi MC, Besson F, Dosset P, Milhiet PE, Le GC (2007) Remodeling of ordered membrane domains by GPI-anchored intestinal alkaline phosphatase. Langmuir 23:9358–9364

    Article  PubMed  CAS  Google Scholar 

  563. Sesana S, Re F, Bulbarelli A, Salerno D, Cazzaniga E, Masserini M (2008) Membrane features and activity of GPI-anchored enzymes: alkaline phosphatase reconstituted in model membranes. Biochemistry USA 47:5433–5440

    Article  CAS  Google Scholar 

  564. Srivastava AK, Masinde G, Yu H, Baylink DJ, Mohan S (2004) Mapping quantitative trait loci that influence blood levels of alkaline phosphatase in MRL/MpJ and SJL/J mice. Bone 35:1086–1094

    Article  PubMed  CAS  Google Scholar 

  565. Moss DW (1992) Perspectives in alkaline phosphatase research. Clin Chem 38:2486–2492

    PubMed  CAS  Google Scholar 

  566. Moss DW (1994) Release of membrane-bound enzymes from cells and the generation of isoforms. Clin Chim Acta 226:131–142

    Article  PubMed  CAS  Google Scholar 

  567. Magnusson P, Sharp CA, Farley JR (2002) Different distributions of human bone alkaline phosphatase isoforms in serum and bone tissue extracts. Clin Chim Acta 325:59–70

    Article  PubMed  CAS  Google Scholar 

  568. Low MG, Huang KS (1991) Factors affecting the ability of glycosylphosphatidylinositol- specific phospholipase-D to degrade the membrane anchors of cell surface proteins. Biochem J 279:483–493

    PubMed  CAS  Google Scholar 

  569. Anh DJ, Eden A, Farley JR (2001) Quantitation of soluble and skeletal alkaline phosphatase, and insoluble alkaline phosphatase anchor-hydrolase activities in human serum. Clin Chim Acta 311:137–148

    Article  PubMed  CAS  Google Scholar 

  570. Brocklehurst D, Wilde CE, Doar JW (1978) The incidence and likely origins of serum particulate alkaline phosphatase and lipoprotein-X in liver disease. Clin Chim Acta 88:509–515

    Article  PubMed  CAS  Google Scholar 

  571. De Broe ME, Roels F, Nouwen EJ, Claeys L, Wieme RJ (1985) Liver plasma membrane: the source of high molecular weight alkaline phosphatase in human serum. Hepatol 5:118–128

    Article  Google Scholar 

  572. Nakano T, Inoue I, Alpers DH, Akiba Y, Katayama S, Shinozaki R, Kaunitz JD, Ohshima S, Akita M, Takahashi S, Koyama I, Matsushita M, Komoda T (2009) Role of lysophosphatidylcholine in brush-border intestinal alkaline phosphatase release and restoration. Amer J Physiol Gastrointest L 297:G207–G214

    Article  CAS  Google Scholar 

  573. Vittur F, Stagni N, Moro L, de Bernhard B (1984) Alkaline phosphatase binds to collagen; a hypothesis on the mechanism of extravesicular mineralization in epiphyseal cartilage. Experientia 40:836–837

    Article  PubMed  CAS  Google Scholar 

  574. Wu LN, Genge BR, Lloyd GC, Wuthier RE (1991) Collagen-binding proteins in collagenase-released matrix vesicles from cartilage. Interaction between matrix vesicle proteins and different types of collagen. J Biol Chem 266:1195–1203

    PubMed  CAS  Google Scholar 

  575. Wu LN, Genge BR, Wuthier RE (1992) Evidence for specific interaction between matrix vesicle proteins and the connective tissue matrix. Bone Miner 17:247–252

    Article  PubMed  CAS  Google Scholar 

  576. Tsonis PA, Argraves WS, Millán JL (1988) A putative functional domain of human placental alkaline phosphatase predicted from sequence comparisons. Biochem J 254:623–624

    PubMed  CAS  Google Scholar 

  577. Bossi M, Hoylaerts MF, Millán JL (1993) Modifications in a flexible surface loop modulate the isozyme-specific properties of mammalian alkaline phosphatases. J Biol Chem 268:25409–25416

    PubMed  CAS  Google Scholar 

  578. Mornet E, Stura E, Lia-Baldini AS, Stigbrand T, Menez A, Le Du MH (2001) Structural evidence for a functional role of human tissue nonspecific alkaline phosphatase in bone mineralization. J Biol Chem 276:31171–31178

    Article  PubMed  CAS  Google Scholar 

  579. Makiya R, Stigbrand T (1992) Placental alkaline phosphatase has a binding site for the human immunoglobulin-G Fc portion. Eur J Biochem 205:341–345

    Article  PubMed  CAS  Google Scholar 

  580. Makiya R, Thornell LE, Stigbrand T (1992) Placental alkaline phosphatase, a GPI-anchored protein, is clustered in clathrin-coated vesicles. Biochem Biophys Res Commun 183:803–808

    Article  PubMed  CAS  Google Scholar 

  581. Leathers VL, Norman AW (1993) Evidence for calcium mediated conformational changes in calbindin-D28K (the vitamin D-induced calcium binding protein) interactions with chick intestinal brush border membrane alkaline phosphatase as studied via photoaffinity labeling techniques. J Cell Biochem 52:243–252

    Article  PubMed  CAS  Google Scholar 

  582. Shinozaki T, Watanabe H, Takagishi K, Pritzker KP (1998) Allotype immunoglobulin enhances alkaline phosphatase activity: implications for the inflammatory response. J Lab Clin Med 132:320–328

    Article  PubMed  CAS  Google Scholar 

  583. She QB, Mukherjee JJ, Chung T, Kiss Z (2000) Placental alkaline phosphatase, insulin, and adenine nucleotides or adenosine synergistically promote long-term survival of serum-starved mouse embryo and human fetus fibroblasts. Cell Signal 12:659–665

    Article  PubMed  CAS  Google Scholar 

  584. Kermer V, Ritter M, Albuquerque B, Leib C, Stanke M, Zimmermann H (2010) Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation. Neurosci Lett 485:208–211

    Article  PubMed  CAS  Google Scholar 

  585. Millán JL (1988) Oncodevelopmental expression and structure of alkaline phosphatase genes. Anticancer Res 8:995–1004

    PubMed  Google Scholar 

  586. Kim EE, Wyckoff HW (1991) Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. J Mol Biol 218:449–464

    Article  PubMed  CAS  Google Scholar 

  587. Lazzaroni JC, Atlan D, Portalier RC (1985) Excretion of alkaline phosphatase by Escherichia coli K-12 pho constitutive mutants transformed with plasmids carrying the alkaline phosphatase structural gene. J Bacteriol 164:1376–1380

    PubMed  CAS  Google Scholar 

  588. Sone M, Kishigami S, Yoshihisa T, Ito K (1997) Roles of disulfide bonds in bacterial alkaline phosphatase. J Biol Chem 272:6174–6178

    Article  PubMed  CAS  Google Scholar 

  589. Hulett FM, Kim EE, Bookstein C, Kapp NV, Edwards CW, Wyckoff HW (1991) Bacillus subtilis alkaline phosphatases III and IV. Cloning, sequencing, and comparisons of deduced amino acid sequence with Escherichia coli alkaline phosphatase three-dimensional structure. J Biol Chem 266:1077–1084

    PubMed  CAS  Google Scholar 

  590. Murphy JE, Kantrowitz ER (1994) Why are mammalian alkaline phosphatases much more active than bacterial alkaline phosphatases? Mol Microbiol 12:351–357

    Article  PubMed  CAS  Google Scholar 

  591. Wende A, Johansson P, Vollrath R, Dyall-Smith M, Oesterhelt D, Grininger M (2010) Structural and biochemical characterization of a halophilic archaeal alkaline phosphatase. J Mol Biol 400:52–62

    Article  PubMed  CAS  Google Scholar 

  592. Helland R, Larsen RL, Asgeirsson B (2009) The 1.4 Å crystal structure of the large and cold-active Vibrio sp. alkaline phosphatase. Biochim Biophys Acta 1794:297–308

    PubMed  CAS  Google Scholar 

  593. Kozlenkov A, Le Du MH, Cuniasse P, Ny T, Hoylaerts MF, Millán JL (2004) Residues determining the binding specificity of uncompetitive inhibitors to tissue-nonspecific alkaline phosphatase. J Bone Miner Res 19:1862–1872

    Article  PubMed  CAS  Google Scholar 

  594. Llinas P, Stura EA, Menez A, Kiss Z, Stigbrand T, Millán JL, Le Du MH (2005) Structural studies of human placental alkaline phosphatase in complex with functional ligands. J Mol Biol 350:441–451

    Article  PubMed  CAS  Google Scholar 

  595. Holtz KM, Kantrowitz ER (1999) The mechanism of the alkaline phosphatase reaction: insights from NMR, crystallography and site-specific mutagenesis. FEBS Lett 462:7–11

    Article  PubMed  CAS  Google Scholar 

  596. Schwartz JH, Lipmann F (1961) Phosphate incorporation into alkaline phosphatase of E. coli. Proc Natl Acad Sci USA 47:1996–2005

    Article  PubMed  CAS  Google Scholar 

  597. Kim EE, Wyckoff HW (1990) Structure of alkaline phosphatases. Clin Chim Acta 186:175–187

    Article  PubMed  CAS  Google Scholar 

  598. Holtz KM, Stec B, Kantrowitz ER (1999) A model of the transition state in the alkaline phosphatase reaction. J Biol Chem 274:8351–8354

    Article  PubMed  CAS  Google Scholar 

  599. Le Du MH, Lamoure C, Muller BH, Bulgakov OV, Lajeunesse E, Menez A, Boulain JC (2002) Artificial evolution of an enzyme active site: structural studies of three highly active mutants of Escherichia coli alkaline phosphatase. J Mol Biol 316:941–953

    Article  PubMed  CAS  Google Scholar 

  600. Wang J, Kantrowitz ER (2006) Trapping the tetrahedral intermediate in the alkaline phosphatase reaction by substitution of the active site serine with threonine. Protein Sci 15:2395–2401

    Article  PubMed  CAS  Google Scholar 

  601. Andrews LD, Deng H, Herschlag D (2011) Isotope-edited FTIR of alkaline phosphatase resolves paradoxical ligand binding properties and suggests a role for ground-state destabilization. J Am Chem Soc 133:11621–11631

    Article  PubMed  CAS  Google Scholar 

  602. López-Canut V, Roca M, Bertrán J, Moliner V, Tuñón I (2011) Promiscuity in alkaline phosphatase superfamily. Unraveling evolution through molecular simulations. J Am Chem Soc 133:12050–12062

    Article  PubMed  CAS  Google Scholar 

  603. Jones SR, Kindman LA, Knowles JR (1978) Stereochemistry of phosphoryl group transfer using a chiral [16O, 17O, 18O] stereochemical course of alkaline phosphatase. Nature 275:564–565

    Article  PubMed  CAS  Google Scholar 

  604. Hull WE, Halford SE, Gutfreund H, Sykes BD (1976) 31P nuclear magnetic resonance study of alkaline phosphatase: the role of inorganic phosphate in limiting the enzyme turnover rate at alkaline pH. Biochemistry USA 15:1547–1561

    Article  CAS  Google Scholar 

  605. Otvos JD, Alger JR, Coleman JE, Armitage IM (1979) 31P NMR of alkaline phosphatase. Saturation transfer and metal–phosphorus coupling. J Biol Chem 254:1778–1780

    PubMed  CAS  Google Scholar 

  606. Gettins P, Coleman JE (1983) 31P nuclear magnetic resonance of phosphoenzyme intermediates of alkaline phosphatase. J Biol Chem 258:408–416

    PubMed  CAS  Google Scholar 

  607. Gettins P, Coleman JE (1984) Zn(II)–113Cd(II) and Zn(II)–Mg(II) hybrids of alkaline phosphatase. 31P and 113Cd NMR. J Biol Chem 259:4991–4997

    PubMed  CAS  Google Scholar 

  608. Gettins P, Metzler M, Coleman JE (1985) Alkaline phosphatase. 31P NMR probes of the mechanism. J Biol Chem 260:2875–2883

    PubMed  CAS  Google Scholar 

  609. Xu X, Kantrowitz ER (1993) Binding of magnesium in a mutant Escherichia coli alkaline phosphatase changes the rate-determining step in the reaction mechanism. Biochemistry USA 32:10683–10691

    Article  CAS  Google Scholar 

  610. Tibbitts TT, Murphy JE, Kantrowitz ER (1996) Kinetic and structural consequences of replacing the aspartate bridge by asparagine in the catalytic metal triad of Escherichia coli alkaline phosphatase. J Mol Biol 257:700–715

    Article  PubMed  CAS  Google Scholar 

  611. Stec B, Holtz KM, Kantrowitz ER (2000) A revised mechanism for the alkaline phosphatase reaction involving three metal ions. J Mol Biol 299:1303–1311

    Article  PubMed  CAS  Google Scholar 

  612. Han R, Coleman JE (1995) Dependence of the phosphorylation of alkaline phosphatase by phosphate monoesters on the pKa of the leaving group. Biochemistry USA 34:4238–4245

    Article  CAS  Google Scholar 

  613. Stec B, Hehir MJ, Brennan C, Nolte M, Kantrowitz ER (1998) Kinetic and X-ray structural studies of three mutant E. coli alkaline phosphatases: insights into the catalytic mechanism without the nucleophile Ser102. J Mol Biol 277:647–662

    Article  PubMed  CAS  Google Scholar 

  614. Sträter N, Lipscomb WN, Klabunde T, Krebs B (1996) Two-metal ion catalysis in enzymatic acyl- and phosphoryl-transfer reactions. Angew Chem Int Ed 35:2024–2055

    Article  Google Scholar 

  615. Butler-Ransohoff JE, Rokita SE, Kendall D, Banzon JA, Carano KS, Kaiser ET, Matlin AR (1992) Active-site mutagenesis of E. coli alkaline phosphatase: replacement of serine-102 with nonnucleophilic amino acids. J Org Chem 57:142–145

    Article  CAS  Google Scholar 

  616. Chaidaroglou A, Brezinski DJ, Middleton SA, Kantrowitz ER (1988) Function of arginine-166 in the active site of Escherichia coli alkaline phosphatase. Biochemistry USA 27:8338–8343

    Article  CAS  Google Scholar 

  617. Stevens CR, Williams RB, Farrell AJ, Blake DR (1991) Hypoxia and inflammatory synovitis: observations and speculation. Ann Rheum Dis 50:124–132

    Article  PubMed  CAS  Google Scholar 

  618. Bevan S, Geppetti P (1994) Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci 17:509–512

    Article  PubMed  CAS  Google Scholar 

  619. Notredame C, Higgins DG, Heringa J (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205–217

    Article  PubMed  CAS  Google Scholar 

  620. Tamao Y, Noguchi K, Sakai-Tomita Y, Hama H, Shimamoto T, Kanazawa H, Tsuda M, Tsuchiya T (1991) Sequence analysis of nutA gene encoding membrane-bound Cl-dependent 5′-nucleotidase of Vibrio parahaemolyticus. J Biochem 109:24–29

    PubMed  CAS  Google Scholar 

  621. Liyou N, Hamilton S, Elvin C, Willadsen P (1999) Cloning and expression of ecto-5′-nucleotidase from the cattle tick Boophilus microplus. Insect Mol Biol 8:257–266

    Article  PubMed  CAS  Google Scholar 

  622. Caljon G, De Ridder K, De Baetselier P, Coosemans M, Van Den Abbeele J (2010) Identification of a tsetse fly salivary protein with dual inhibitory action on human platelet aggregation. PLoS One 5:e9671

    Article  PubMed  CAS  Google Scholar 

  623. Mans BJ, Gasper AR, Louw AI, Neitz AW (1998) Purification and characterization of apyrase from the tick, Ornithodoros savignyi. Comp Biochem Physiol B Biochem Mol Biol 120:617–624

    Article  PubMed  CAS  Google Scholar 

  624. Gounaris K, Selkirk ME, Sadeghi SJ (2004) A nucleotidase with unique catalytic properties is secreted by Trichinella spiralis. Mol Biochem Parasitol 136:257–264

    Article  PubMed  CAS  Google Scholar 

  625. Oda Y, Kuo MD, Huang SS, Huang JS (1991) The plasma cell membrane glycoprotein, PC-1, is a threonine-specific protein kinase stimulated by acidic fibroblast growth factor. J Biol Chem 266:16791–16795

    PubMed  CAS  Google Scholar 

  626. North EJ, Howard AL, Wanjala IW, Pham TCT, Baker DL, Parrill AL (2010) Pharmacophore development and application toward the identification of novel, small-molecule autotaxin inhibitors. J Med Chem 53:3095–3105

    Article  PubMed  CAS  Google Scholar 

  627. Schuster-Böckler B, Schultz J, Rahmann S (2004) HMM logos for visualization of protein families. BMC Bioinformatics 5:7

    Article  PubMed  Google Scholar 

  628. Drosopoulos JHF (2002) Roles of Asp54 and Asp213 in Ca2+ utilization by soluble human CD39/ecto-nucleotidase. Arch Biochem Biophys 406:85–95

    Article  PubMed  CAS  Google Scholar 

  629. Hicks-Berger CA, Yang F, Smith TM, Kirley TL (2001) The importance of histidine residues in human ecto-nucleoside triphosphate diphosphohydrolase-3 as determined by site-directed mutagenesis. BBA Protein Struct Mol Enzym 1547:72–81

    Article  CAS  Google Scholar 

  630. Kirley TL, Yang F, Ivanenkov VV (2001) Site-directed mutagenesis of human nucleoside triphosphate diphosphohydrolase 3: the importance of conserved glycine residues and the identification of additional conserved protein motifs in eNTPDases. Arch Biochem Biophys 395:94–102

    Article  PubMed  CAS  Google Scholar 

  631. Wu J, Hansen GH, Nilsson A, Duan RD (2005) Functional studies of human intestinal alkaline sphingomyelinase by deglycosylation and mutagenesis. Biochem J 386:153–160

    Article  PubMed  CAS  Google Scholar 

  632. Stec B, Cheltsov A, Millán JL (2010) Refined structures of placental alkaline phosphatase show a consistent pattern of interactions at the peripheral site. Acta Crystallogr Sect F Struct Biol Cryst Commun 66:866–870

    Article  PubMed  CAS  Google Scholar 

  633. de Backer M, McSweeney S, Rasmussen HB, Riise BW, Lindley P, Hough E (2002) The 1.9 A crystal structure of heat-labile shrimp alkaline phosphatase. J Mol Biol 318:1265–1274

    Article  PubMed  CAS  Google Scholar 

  634. de Backer MME, McSweeney S, Lindley PF, Hough E (2004) Ligand-binding and metal-exchange crystallographic studies on shrimp alkaline phosphatase. Acta Crystallogr D Biol Cryst 60:1555–1561

    Article  CAS  Google Scholar 

  635. Tsuruta H, Mikami B, Higashi T, Aizono Y (2010) Crystal structure of cold-active alkaline phosphatase from the Psychrophile shewanella sp. Biosci Biotechnol Biochem 74:69–74

    Article  PubMed  CAS  Google Scholar 

  636. Wang E, Koutsioulis D, Leiros HK, Andersen OA, Bouriotis V, Hough E, Heikinheimo P (2007) Crystal structure of alkaline phosphatase from the Antarctic bacterium TAB5. J Mol Biol 366:1318–1331

    Article  PubMed  CAS  Google Scholar 

  637. Butler-Ransohoff JE, Kendall DA, Kaiser ET (1988) Use of site-directed mutagenesis to elucidate the role of arginine-166 in the catalytic mechanism of alkaline phosphatase. Proc Natl Acad Sci USA 85:4276–4278

    Article  PubMed  CAS  Google Scholar 

  638. Chaidaroglou A, Kantrowitz ER (1989) Alteration of aspartate 101 in the active site of Escherichia coli alkaline phosphatase enhances the catalytic activity. Protein Eng 3:127–132

    Article  PubMed  CAS  Google Scholar 

  639. Mandecki W, Shallcross MA, Sowadski J, Tomazic-Allen S (1991) Mutagenesis of conserved residues within the active site of Escherichia coli alkaline phosphatase yields enzymes with increased kcat. Protein Eng 4:801–804

    Article  PubMed  CAS  Google Scholar 

  640. Chen L, Neidhart D, Kohlbrenner WM, Mandecki W, Bell S, Sowadski J, Abad-Zapatero C (1992) 3-D structure of a mutant (Asp101→Ser) of E. coli alkaline phosphatase with higher catalytic activity. Protein Eng 5:605–610

    Article  PubMed  CAS  Google Scholar 

  641. Dealwis CG, Chen L, Brennan C, Mandecki W, Abad-Zapatero C (1995) 3-D structure of the D153G mutant of Escherichia coli alkaline phosphatase: an enzyme with weaker magnesium binding and increased catalytic activity. Protein Eng 8:865–871

    Article  PubMed  CAS  Google Scholar 

  642. Xu X, Kantrowitz ER (1991) A water-mediated salt link in the catalytic site of Escherichia coli alkaline phosphatase may influence activity. Biochemistry USA 30:7789–7796

    Article  CAS  Google Scholar 

  643. Kahya N, Brown DA, Schwille P (2005) Raft partitioning and dynamic behavior of human placental alkaline phosphatase in giant unilamellar vesicles. Biochemistry USA 44:7479–7489

    Article  CAS  Google Scholar 

  644. Matoba K, Shiba T, Takeuchi T, Sibley LD, Seiki M, Kikyo F, Horiuchi T, Asai T, Haradaa S (2010) Crystallization and preliminary X-ray structural analysis of nucleoside triphosphate hydrolases from Neospora caninum and Toxoplasma gondii. Acta Crystallogr Sect F Struct Biol Cryst Commun 66:1445–1448

    Google Scholar 

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Acknowledgments

The research work of the authors was supported by the Deutsche Forschungsgemeinschaft (to HZ: 140/17-4; Zi 140/18-1 and to NS: Str 477/11, Str 477/12, Str 477/13).

Author information

Authors and Affiliations

  1. Institute of Cell Biology and Neuroscience, Molecular and Cellular Neurobiology, Biologicum, Goethe-University Frankfurt, Max-von-Laue-Str. 13, 60438, Frankfurt am Main, Germany

    Herbert Zimmermann

  2. Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK

    Matthias Zebisch

  3. Center for Biotechnology and Biomedicine, Institute of Bioanalytical Chemistry, University of Leipzig, Leipzig, Germany

    Norbert Sträter

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  1. Herbert Zimmermann
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  2. Matthias Zebisch
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  3. Norbert Sträter
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Correspondence to Herbert Zimmermann.

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Zimmermann, H., Zebisch, M. & Sträter, N. Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signalling 8, 437–502 (2012). https://doi.org/10.1007/s11302-012-9309-4

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  • DOI: https://doi.org/10.1007/s11302-012-9309-4

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