First Author | Myers MD | Year | 2006 |
Journal | Nat Immunol | Volume | 7 |
Issue | 1 | Pages | 57-66 |
PubMed ID | 16327786 | Mgi Jnum | J:112388 |
Mgi Id | MGI:3656190 | Doi | 10.1038/ni1291 |
Citation | Myers MD, et al. (2006) Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex. Nat Immunol 7(1):57-66 |
abstractText | 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 CD3epsilon. This required multiple domains in SLAP and the ring finger of c-Cbl. Furthermore, expression of SLAP and c-Cbl together induced TCRzeta 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. |