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
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