PathwayStep6526 PathwayStep6527 PathwayStep6525 PathwayStep6528 Dephosphorylation of CD3-zeta by PD-1 bound phosphatases PD-1 binds B7DC and B7H1 Phosphorylation of PD-1 Interaction of SHP-1 or SHP-2 with phospho PD-1 PD-1 signaling Authored: Garapati, P V, 2008-12-16 11:12:19 Edited: Garapati, P V, 2008-12-16 11:12:19 Pubmed18173375 Pubmed18759926 Reactome Database ID Release 43389948 Reactome, http://www.reactome.org ReactomeREACT_19324 Reviewed: Bluestone, JA, Esensten, J, 2009-06-01 18:47:33 The Programmed cell death protein 1 (PD-1) is one of the negative regulators of TCR signaling. PD-1 may exert its effects on cell differentiation and survival directly by inhibiting early activation events that are positively regulated by CD28 or indirectly through IL-2. PD-1 ligation inhibits the induction of the cell survival factor Bcl-xL and the expression of transcription factors associated with effector cell function, including GATA-3, Tbet, and Eomes. PD-1 exerts its inhibitory effects by bringing phosphatases SHP-1 and SHP-2 into the immune synapse, leading to dephosphorylation of CD3-zeta chain, PI3K and AKT.