PathwayStep6520 PathwayStep6521 PathwayStep6518 PathwayStep6517 PathwayStep6519 Phosphorylation of CTLA-4 SHP2 phosphatase binds CTLA-4 Dephosphorylation of AKT by PP2A PP2A binds CTLA4 homodimer CTLA-4 binds B7-1/B7-2 CTLA4 inhibitory signaling Authored: Garapati, P V, 2008-12-16 11:12:19 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.?<br>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. Edited: Garapati, P V, 2008-12-16 11:12:19 Pubmed10374692 Pubmed11905831 Pubmed12876557 Pubmed16551244 Reactome Database ID Release 43389513 Reactome, http://www.reactome.org ReactomeREACT_19405 Reviewed: Bluestone, JA, Esensten, J, 2009-06-01 18:47:33