Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Antigens, CD28, Carrier Proteins, Cells, Cultured, Humans, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphatidylinositol 3-Kinases, Phosphoproteins, Protein Transport, Proto-Oncogene Proteins c-cbl, Receptors, Antigen, T-Cell, T-Lymphocytes, Ubiquitin-Protein Ligases, Ubiquitins
Adaptor Proteins, Signal Transducing, Animals, Antigens, CD28, Carrier Proteins, Cells, Cultured, Humans, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphatidylinositol 3-Kinases, Phosphoproteins, Protein Transport, Proto-Oncogene Proteins c-cbl, Receptors, Antigen, T-Cell, T-Lymphocytes, Ubiquitin-Protein Ligases, Ubiquitins
Nat. Immunol.
Date: Sep. 01, 2001
PubMed ID: 11526404
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