Restoration of Thymocyte Development and Function in zap-70−/− Mice by the Syk Protein Tyrosine Kinase

The Syk family of protein tyrosine kinases, consisting of ZAP-70 and Syk, associate with the pre- and αβ T cell antigen receptors (TCRs) and undergo tyrosine phosphorylation and activation following receptor engagement. Thymocyte development in zap-70−/− mice is blocked at the CD4+CD8+ TCRlo stage. The presence of Syk in the thymus has raised the possibility that Syk may be able to mediate TCR function. To determine if Syk can play a role in thymocyte development, we generated zap-70−/− mice expressing a human syk cDNA. Syk expression restored both thymocyte development and function. In addition, Syk function required the CD45 transmembrane protein tyrosine phosphatase. Hence, ZAP-70 and Syk can play overlapping functions and exhibit similar regulatory mechanisms in mediating αβ T cell development.