Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells - PubMed (original) (raw)
Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells
D Fang et al. Nat Immunol. 2001 Sep.
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.
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