Reactome | CTLA4 inhibitory signaling

CTLA4 inhibitory signaling

Stable Identifier

R-HSA-389513

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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CTLA4 is one of the best studied inhibitory receptors of the CD28 superfamily. CTLA4 inhibits T cell activation by reducing IL2 production and IL2 expression, and by arresting T cells at the G1 phase of the cell cycle. CTLA-4 expressed by a T cell subpopulation exerts a dominant control on the proliferation of other T cells, which limits autoreactivity. CTLA4 also blocks CD28 signals by competing for the ligands B71 and B72 in the limited space between T cells and antigenpresenting cells. Though the mechanism is obscure, CTLA4 may also propagate inhibitory signals that actively counter those produced by CD28. CTLA4 can also function in a ligand-independent manner.
CTLA-4 regulates the activation of pathogenic T cells by directly modulating T cell receptor signaling (i.e. TCR-zeta chain phosphorylation) as well as downstream biochemical signals (i.e. ERK activation). The cytoplasmic region of CTLA4 contains a tyrosine motif YVKM and a proline rich region. After TCR stimulation, it undergoes tyrosine phosphorylation by src kinases, inducing surface retention.

Literature References

PubMed ID	Title	Journal	Year
24705298	Protein kinase C-η controls CTLA-4-mediated regulatory T cell function Yates, JR, Becart, S, Saito, T, Casas, J, Canonigo-Balancio, AJ, Kronenberg, M, Kong, KF, Gascoigne, NR, Yokosuka, T, Kim, G, Altman, A, Fu, G, Zhang, Y	Nat Immunol	2014
11905831	T-cell regulation by CD28 and CTLA-4 Frauwirth, KA, Alegre, ML, Thompson, CB	Nat Rev Immunol	2001
16598076	The multifunctional GIT family of proteins Hoefen, RJ, Berk, BC	J Cell Sci	2006
16551244	A molecular perspective of CTLA-4 function Madrenas, J, Teft, WA, Kirchhof, MG	Annu Rev Immunol	2006
12876557	Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling Schneider, H, Rudd, CE	Nat Rev Immunol	2003
10374692	CD28/CTLA-4 and CD80/CD86 families: signaling and function Hutchcroft, JE, Slavik, JM, Bierer, BE	Immunol Res	1999