Upon TCR-CTLA-4 complex formation, CTLA4 is tyrosine phosphorylated. Src family tyrosine kinases Fyn, Lyn, and Lck associate with CTLA-4 and phosphorylate both Y-165 and Y-182 that are mainly responsible for interaction with Fyn through its SH2 domain. Once tyrosine 165 is phosphorylated, PP2A is activated and disassociates from CTLA4; this correlates with T cell inactivation.
Baroja, ML, Vijayakrishnan, L, Bettelli, E, Darlington, PJ, Chau, TA, Ling, V, Collins, M, Carreno, BM, Madrenas, J, Kuchroo, VK
Miyatake, S, Nakaseko, C, Umemori, H, Yamamoto, T, Saito, T
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