Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4
LEM Marengère, P Waterhouse, GS Duncan… - Science, 1996 - science.org
The absence of CTLA-4 results in uncontrolled T cell proliferation. The T cell receptor-
specific kinases FYN, LCK, and ZAP-70 as well as the RAS pathway were found to be
activated in T cells of Ctla-4−/− mutant mice. In addition, CTLA-4 specifically associated with
the tyrosine phosphatase SYP, an interaction mediated by the SRC homology 2 (SH2)
domains of SYP and the phosphotyrosine sequence Tyr-Val-Lys-Met within the CTLA-4
cytoplasmic tail. The CTLA-4-associated SYP had phosphatase activity toward the RAS …
specific kinases FYN, LCK, and ZAP-70 as well as the RAS pathway were found to be
activated in T cells of Ctla-4−/− mutant mice. In addition, CTLA-4 specifically associated with
the tyrosine phosphatase SYP, an interaction mediated by the SRC homology 2 (SH2)
domains of SYP and the phosphotyrosine sequence Tyr-Val-Lys-Met within the CTLA-4
cytoplasmic tail. The CTLA-4-associated SYP had phosphatase activity toward the RAS …
The absence of CTLA-4 results in uncontrolled T cell proliferation. The T cell receptor-specific kinases FYN, LCK, and ZAP-70 as well as the RAS pathway were found to be activated in T cells of Ctla-4−/− mutant mice. In addition, CTLA-4 specifically associated with the tyrosine phosphatase SYP, an interaction mediated by the SRC homology 2 (SH2) domains of SYP and the phosphotyrosine sequence Tyr-Val-Lys-Met within the CTLA-4 cytoplasmic tail. The CTLA-4-associated SYP had phosphatase activity toward the RAS regulator p52SHC. Thus, the RAS pathway and T cell activation through the T cell receptor are regulated by CTLA-4-associated SYP.
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