Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCR[zeta] for degradation

• Published in: The Journal of cell biology 2005, Vol.170 (2), p.285-294
• Main Authors: Myers, Margaret D, Dragone, Leonard L, Weiss, Arthur
• Format: Article
• Language: English
• ISSN: 0021-9525; 1540-8140

Src-like adaptor protein (SLAP) down-regulates expression of the T cell receptor (TCR)-CD3 complex during a specific stage of thymocyte development when the TCR repertoire is selected. Consequently, SLAP-/- thymocytes display alterations in thymocyte development. Here, we have studied the mechanism of SLAP function. We demonstrate that SLAP-deficient thymocytes have increased TCR[zeta] chain expression as a result of a defect in TCR[zeta] degradation. Failure to degrade TCR[zeta] leads to an increased pool of fully assembled TCR-CD3 complexes that are capable of recycling back to the cell surface. We also provide evidence that SLAP functions in a pathway that requires the phosphorylated TCR[zeta] chain and the Src family kinase Lck, but not ZAP-70 ([zeta]-associated protein of 70 kD). These studies reveal a unique mechanism by which SLAP contributes to the regulation of TCR expression during a distinct stage of thymocyte development.