PathwayStep6454 PathwayStep6458 PathwayStep6476 PathwayStep6498 Downstream TCR signaling TCR signaling Authored: Rudd, C.E., de Bono, B, Garapati, P V, 2008-01-24 15:53:10 GENE ONTOLOGYGO:0050852 Pubmed10375551 Pubmed12876557 Pubmed9989491 Reactome Database ID Release 43202403 Reactome, http://www.reactome.org ReactomeREACT_12526 Reviewed: Trowsdale, J, 2008-02-26 12:02:59 The TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen presenting cells (APCs) results in the activation of protein tyrosine kinases (PTKs) that associate with CD3 and TCR zeta subunits and the co-receptor CD4. Members of the Src kinases (Lck), Syk kinases (ZAP-70), Tec (Itk) and Csk families of nonreceptor PTKs play a crucial role in T cell activation. Activation of PTKs following TCR engagement results in the recruitment and tyrosine phosphorylation of enzymes such as phospholipase C gamma1 and Vav as well as critical adaptor proteins such as LAT, SLP-76 and Gads. These proximal activation leads to reorganization of the cytoskeleton as well as transcription activation of multiple genes leading to T lymphocyte proliferation, differentiation and/or effector function. Phosphorylation of CD3 and TCR zeta chains Translocation of ZAP-70 to Immunological synapse Generation of second messenger molecules