Abstract
Protein-tyrosine kinases (PTKs) are important regulators of intracellular signal-transduction pathways mediating development and multicellular communication in metazoans. Their activity is normally tightly controlled and regulated. Perturbation of PTK signalling by mutations and other genetic alterations results in deregulated kinase activity and malignant transformation. The lipid kinase phosphoinositide 3-OH kinase (PI(3)K) and some of its downstream targets, such as the protein-serine/threonine kinases Akt and p70 S6 kinase (p70S6K), are crucial effectors in oncogenic PTK signalling. This review emphasizes how oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity and provides an update on our knowledge about the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Humans
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Mutation / genetics
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Neoplasms / enzymology*
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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Oncogene Protein v-akt
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Oncogene Proteins / antagonists & inhibitors
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Oncogenes / genetics
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism
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Retroviridae Proteins, Oncogenic / genetics
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Retroviridae Proteins, Oncogenic / metabolism
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Ribosomal Protein S6 Kinases / genetics
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Ribosomal Protein S6 Kinases / metabolism
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Signal Transduction*
Substances
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Oncogene Proteins
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Retroviridae Proteins, Oncogenic
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Phosphatidylinositol 3-Kinases
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Protein-Tyrosine Kinases
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Receptor Protein-Tyrosine Kinases
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Oncogene Protein v-akt
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Ribosomal Protein S6 Kinases