Abstract
Cbl-b, a ring-type E3 ubiquitin protein ligase, is implicated in setting the threshold of T lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) was identified as a substrate for Cbl-b. We have shown that Cbl-b negatively regulated p85 in a proteolysis-independent manner. Cbl-b is involved in the recruitment of p85 to CD28 and T cell antigen receptor zeta through its E3 ubiquitin ligase activity. The enhanced activation of Cbl-b(-/-) T cells was suppressed by the inhibition of PI3K. The results suggest a proteolysis-independent function for Cbl-b in the modification of protein recruitment.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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CD28 Antigens / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cells, Cultured
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Humans
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Jurkat Cells
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Lymphocyte Activation
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / physiology*
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Protein Transport
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Proto-Oncogene Proteins c-cbl
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocytes / immunology*
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Ubiquitin-Protein Ligases*
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Ubiquitins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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CD28 Antigens
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Carrier Proteins
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Cblb protein, mouse
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Membrane Proteins
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Phosphoproteins
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Receptors, Antigen, T-Cell
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Ubiquitins
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antigen T cell receptor, zeta chain
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CBLB protein, human
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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Phosphatidylinositol 3-Kinases