Multiple kinases mediate T-cell-receptor signaling.

T-cell-receptor stimulation results in an array of early responses similar to those evoked by activation of receptor tyrosine kinases, including rapid induction of tyrosine phosphorylation, although no tyrosine kinase activity resides within any of the chains of the T-cell receptor. However, a 70 kDa tyrosine kinase, ZAP-70, has been found to associate with the zeta and CD3 chains of the T-cell receptor following stimulation. Recently, several immunodeficient individuals have been identified with loss-of-function mutations of ZAP-70. T cells from these patients have impaired responses to T-cell-receptor ligands, implying a central role for ZAP-70 in T-cell signaling. Here we examine the likely interactions of ZAP-70 and Src family kinases in generating a T-cell response.