Reactome | CTLA4 inhibitory signaling

CTLA4 inhibitory signaling

Stable Identifier

R-HSA-389513

Type

Pathway

Species

Homo sapiens

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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
16551244	A molecular perspective of CTLA-4 function Teft, WA, Kirchhof, MG, Madrenas, J	Annu Rev Immunol	2006
11905831	T-cell regulation by CD28 and CTLA-4 Alegre, ML, Frauwirth, KA, Thompson, CB	Nat Rev Immunol	2001
12876557	Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling Rudd, CE, Schneider, H	Nat Rev Immunol	2003
10374692	CD28/CTLA-4 and CD80/CD86 families: signaling and function Slavik, JM, Hutchcroft, JE, Bierer, BE	Immunol Res	1999