Fang D, Liu Y C
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Nat Immunol. 2001 Sep;2(9):870-5. doi: 10.1038/ni0901-870.
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.
Cbl-b是一种环状E3泛素蛋白连接酶，与设定T淋巴细胞激活阈值有关。磷脂酰肌醇3激酶（PI3K）的p85调节亚基被确定为Cbl-b的底物。我们已经表明，Cbl-b以不依赖蛋白水解的方式对p85进行负调控。Cbl-b通过其E3泛素连接酶活性参与将p85募集到CD28和T细胞抗原受体ζ。PI3K的抑制可抑制Cbl-b基因敲除（Cbl-b(-/-)）T细胞的增强激活。结果表明Cbl-b在蛋白质募集修饰中具有不依赖蛋白水解的功能。
