The Src-related protein tyrosine kinases Lck p56 and Fyn p59 are critically involved in T cell antigen receptor (TCR)/CD3-triggered activation. T lymphocytes also express a second class of non-receptor protein tyrosine kinases which includes Syk p70 and ZAP p72. These kinases resemble the Src family protein tyrosine kinases in that they have a C-terminal catalytic domain, but differ in that they are characterized by two SH2 domains but no SH3 domains. Evidence for the involvement of the Syk/ZAP family proteins in T cell activation was suggested by the finding that Syk p72 kinase fused to the transmembrane and extracellular domains of CD7 and DC16, respectively, can induce complete T cell activation. In contrast, the ZAP p70 kinase was insufficient unless it was coaggregated with a Fyn p59-containing chimera,suggesting that regulation of ZAP p70 activity may require a functional interaction with Src family kinases.