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Restoration of thymocyte development and function in zap-70-/- mice by the Syk protein tyrosine kinase
1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The Syk family of protein tyrosine kinases, consisting of ZAP-70 and Syk, associate with the pre- and alphabeta 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+ TCR(lo) 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 alphabeta T cell development.
The Syk family of protein tyrosine kinases, consisting of ZAP-70 and Syk, associate with the pre- and alphabeta 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+ TCR(lo) 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 alphabeta T cell development.