ZAP70 (Tyrosine-protein kinase ZAP-70, phospho Zap70) is a protein tyrosine kinase (PTK) that associates with the z subunit of the T cell antigen receptor (TCR) and undergoes tyrosine phosphorylation following TCR stimulation. Following TCR engagement, Zap-70 is rapidly phosphorylated on several tyrosine residues through autophosphorylation and transphosphorylation by the Src family tyrosine kinase Lck. ZAP70 contains two SH2-like domains with the PTK domain located at the C-terminus. It appears that both phospho Zap70 and Syk are recruited to the phosphorylated CD3 and z subunits after TCR stimulation. Phosphorylation of Tyr319 is required for the assembly of a phospho Zap70-containing signaling complex that leads to the activation of the PLC-gamma1-dependent and Ras-dependent signaling cascades in antigen-stimulated T cells. The orthologous Tyr352 residue in Syk is also involved in the association with PLC-gamma1.