Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex
Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex
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DOI：
10.1038/ni1291
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发表时间：
2006-01-01
影响因子：
30.5
通讯作者：
Weiss, A
中科院分区：
文献类型：
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作者：
Myers, MD;Sosinowski, T;Weiss, A
衔接子分子Sb 2和E3泛素连接酶c-Cbl各自调节胸腺细胞上T细胞受体（TCR）-CD 3的表达。在这里，我们提供了遗传和生物化学证据，表明这两种分子在同一途径中发挥作用。TCR-⑶ 3表达在不存在S细胞和/或c-Cbl的情况下相似。发现SbR和c-Cbl相互作用，并且它们的表达一起下调CD 3+。这需要多个领域的SNOW和环指的c-Cbl。此外，表达的SbR和c-Cbl一起诱导TCR zeta泛素化和降解，防止完全组装的回收TCR复合物的积累。这些研究表明，SHBE将c-Cbl的E3连接酶活性与TCR连接，从而允许TCR表达的阶段特异性调节。
The adaptor molecule SLAP and E3 ubiquitin ligase c-Cbl each regulate expression of T cell receptor (TCR)-CD3 on thymocytes. Here we provide genetic and biochemical evidence that both molecules function in the same pathway. TCR-CD3 expression was similar in the absence of SLAP and/or c-Cbl. SLAP and c-Cbl were found to interact, and their expression together downregulated CD3 epsilon. This required multiple domains in SLAP and the ring finger of c-Cbl. Furthermore, expression of SLAP and c-Cbl together induced TCR zeta ubiquitination and degradation, preventing the accumulation of fully assembled recycling TCR complexes. These studies indicate that SLAP links the E3 ligase activity of c-Cbl to the TCR, allowing for stage-specific regulation of TCR expression.