Reactome | Phosphorylation of CTLA-4

Phosphorylation of CTLA-4

Stable Identifier

R-HSA-388833

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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Upon TCR engagement, CTLA4 undergoes tyrosine phosphorylation mediated by Src family kinases, including Fyn, Lyn, and Lck. These kinases phosphorylate key tyrosine residues, specifically Y201 and Y218, enabling interaction with Fyn through its SH2 domain (Marengere et al. 1996). Additionally, phosphorylation of Y165 on CTLA4 triggers the activation of protein phosphatase 2A (PP2A), which subsequently dissociates from CTLA4. This dissociation of PP2A is associated with the inhibition of T cell activation, highlighting the regulatory role of CTLA4 in modulating T cell responses (Baroja et al. 2002).

Literature References

PubMed ID	Title	Journal	Year
9712716	Src family tyrosine kinases associate with and phosphorylate CTLA-4 (CD152) Nakaseko, C, Yamamoto, T, Miyatake, S, Umemori, H, Saito, T	Biochem Biophys Res Commun	1998
11994459	Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A Darlington, PJ, Vijayakrishnan, L, Madrenas, J, Baroja, ML, Collins, M, Ling, V, Carreno, BM, Chau, TA, Bettelli, E, Kuchroo, VK	J Immunol	2002
8638161	Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4 Waterhouse, P, Mittrücker, HW, Marengère, LE, Feng, GS, Duncan, GS, Mak, TW	Science	1996