Reactome: A Curated Pathway Database

CTLA4 inhibitory signaling (R-HSA-389513)

Species Homo sapiens

Summation

CTLA4 is one of the best studied inhibitory receptors of the CD28 superfamily. CTLA4 inhibits Tcell 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.

Locations in the PathwayBrowser
Cross References
Database Identifier
BioModels Database BIOMD0000000468
Literature References
pubMedId Title Journal Year
10374692 CD28/CTLA-4 and CD80/CD86 families: signaling and function Immunol Res 1999
11905831 T-cell regulation by CD28 and CTLA-4 Nat Rev Immunol 2001
12876557 Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling Nat Rev Immunol 2003
16551244 A molecular perspective of CTLA-4 function Annu Rev Immunol 2006