LAT Signalosome Antibody Sampler Kit #82703

T cells are activated through a complex signaling transduction pathway that is induced when antigen-presenting cells (APCs) bring antigenic peptides into contact with T cell receptors (TCRs). Upon TCR engagement, activated Zap-70 phosphorylates multiple proteins at conserved tyrosine residues within SH2 binding motifs, exposing these motifs as the docking sites for downstream signaling targets (1,2). Zap-70-mediated phosphorylation of the scaffolding protein LAT at Tyr171 and Tyr220 recruits PLC gamma1 and the adaptor proteins GADS and SLP-76, which bind through their SH2 domain and translocate to the plasma membrane (1-3). Phosphorylation of LAT at Tyr161 creates an additional docking site for PLC gamma1. However, this is delayed relative to other phosphorylation events and may allow the TCR to effectively discriminate between autoantigens and foreign antigens (4). PLC gamma1, which is activated by phosphorylation at Thr783, hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate two secondary messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) (5,6). IP3 and DAG mediate their downstream effects and ultimately activate the transcription factors NFAT, AP-1, and NF-kappaB, which are necessary for T cell proliferation and differentiation into effector cells (7-9). Following TCR ligation, hematopoietic progenitor kinase 1 (HPK1) phosphorylates GADS at Thr262 and SLP-76 at Ser376 (10-12). These phosphorylation events promote GADS and SLP-76 binding to 14-3-3 proteins and detachment from the LAT complex, preventing further TCR signaling (10-12).