RT Journal Article
SR Electronic
T1 Regulation of T Cell Receptor Signaling by Tyrosine Phosphatase SYP Association with CTLA-4
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1170
OP 1173
DO 10.1126/science.272.5265.1170
VO 272
IS 5265
A1 Marengère, Luc E. M.
A1 Waterhouse, Paul
A1 Duncan, Gordon S.
A1 Mittrücker, Hans-Willi
A1 Feng, Gen-Sheng
A1 Mak, Tak W.
YR 1996
UL http://science.sciencemag.org/content/272/5265/1170.abstract
AB 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.