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
11905831 T-cell regulation by CD28 and CTLA-4

Frauwirth, KA, Alegre, ML, Thompson, CB

Nat Rev Immunol 2001
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
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
10374692 CD28/CTLA-4 and CD80/CD86 families: signaling and function

Hutchcroft, JE, Slavik, JM, Bierer, BE

Immunol Res 1999
12876557 Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling

Schneider, H, Rudd, CE

Nat Rev Immunol 2003
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