Phospho-LAT (Tyr161) (E9Q2R) Rabbit mAb #88077

LAT, a transmembrane adaptor protein expressed in T, NK, and mast cells, is an important mediator for T cell receptor (TCR) signaling (1). Upon TCR engagement, activated Zap-70 phosphorylates LAT at multiple conserved tyrosine residues within SH2 binding motifs, exposing these motifs as the docking sites for downstream signaling targets (2,3). The phosphorylation of LAT at Tyr171 and Tyr220 enables the binding of Grb2, Gads/SLP-76, PLCγ1, and PI3 kinase through their SH2 domain and translocates them to the membrane. This process eventually leads to activation of the corresponding signaling pathways (1-4).

Research studies have shown that Zap-70 phosphorylates LAT at Tyr161, which creates an additional docking site to facilitate PLCγ1 recruitment, phosphorylation, and activation (3-5). Tyr161 is a relatively poor substrate for Zap-70 and following TCR engagement, phosphorylation of LAT at Tyr161 is delayed relative to the other distal tyrosine residues. Given the importance of PLCγ1 in regulating multiple T cell effector functions, it is posited that the delayed kinetics of Tyr161 phosphorylation serves as molecular rheostat in order to allow the TCR to effectively discriminate between autoantigens and foreign antigens (6,7).