Requirement for tyrosine residues 315 and 319 within zeta chain-associatedprotein 70 for T cell development

Engagement of the T cell antigen receptor (TCR) induces the transphosphoryl ation of the chain-associated protein of 70,000 Mr (ZAP-70) protein tyrosin e kinase (PTK) by the CD4/8 coreceptor associated Lck PTK. Phosphorylation of Tyr 493 within ZAP-70's activation loop results in the enzymatic activat ion of ZAP-70. Additional tyrosines (Tyrs) within ZAP-70 are phosphorylated that play both positive and negative regulatory roles in TCR function. Pho sphorylation of Tyr residues (Tyrs 315 and 319) within the Interdomain B re gion of the ZAP-70 PTK plays important roles in the generation of second me ssengers after TCP, engagement. Here, we demonstrate that phosphorylation o f these two Tyr residues also play important roles in mediating the positiv e and negative selection of T cells in the thymus.