Zap-70, a Syk family protein tyrosine kinase expressed in T and NK cells, plays a critical role in mediating T cell activation in response to T cell receptor (TCR) engagement. Following TCR engagement, Zap-70 is rapidly phosphorylated on several tyrosine residues, presumably by two mechanisms: autophosphorylation and transphosphorylation by the Src family tyrosine kinase, Lck. Tyrosine phosphorylation of Zap-70 correlates with its increased kinase activity and downstream signaling events.