ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR zeta in murine thymocytes and lymph node T cells.

Studies with T cell lines and clones have shown that engagement of the TCR results in the tyrosine phosphorylation of the TCR subunits. This leads to the recruitment of the ZAP-70 protein tyrosine kinase, an interaction involving the two SH2-domains of ZAP-70 with tyrosine-phosphorylated zeta and CD3. However, as previously described, murine thymocytes and lymph node T cells express a constitutively tyrosine-phosphorylated zeta subunit in the basal state. Here, we show that a fraction of ZAP-70 molecules are constitutively associated with tyrosine-phosphorylated zeta. TCR ligation promotes a large increase in the tyrosine phosphorylation of ZAP-70 as well as other TCR subunits. Genetic studies reveal that the constitutive ZAP-70 association with tyrosine-phosphorylated zeta does not absolutely require either TCR or coreceptor interactions with MHC molecules.

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