T cell receptor signalling

Upon engagement of the TCR by antigen presented on major histocompatibility complex (MHC) molecules, the Src family kinase Lck is activated and proceeds to phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the e, δ, γ and ζ subunits of the TCR. Phosphorylated ITAMs promote the recruitment and subsequent activation of another tyrosine kinase ZAP-70. Two known substrates of ZAP70 are the adapter molecules LAT and SLP-76. Phosphorylation of tyrosine residues on LAT and SLP-76 results in recruitment of a number of other proteins involved in activation of the Ras pathway, calcium mobilization and cytoskeletal reorganization.