Regulation of the p70zap tyrosine protein kinase in T cells by the CD45 phosphotyrosine phosphatase

Abstract

Two classes of protein tyrosine kinases (PTK) are utilized by the T cell antigen receptor (TcR)/CD3 complex for initiation of the signaling cascade, the Src‐family PTK p56^lck and p59^fyn, and the Syk‐family PTK p70^zap and p72^syk. In addition, the CD45 phosphotyrosine phosphatase (PTPase) is required for the induction of tyrosine phosphorylation by the TcR/CD3, presumably by positively regulating Src‐family PTK. Here we report that CD45 also regulates the Syk‐family PTK p70^zap (or ZAP‐70). In CD45‐negative T cells, p70^zap was constitutively phosphorylated on tyrosine and co‐immunoprecipitated with the TcR‐ζ chain. In resting wild‐type CD45‐positive cells, p70^zap was mainly unphosphorylated, but it was rapidly phosphorylated on tyrosine upon treatment of the cells with anti‐CD3 or PTPase inhibitors. Finally, p70^zap co‐distributed with CD45 in intact T cells, and tyrosine phosphorylated p70^zap was dephosphorylated by CD45 in vitro. These findings suggest that CD45 plays an important role, direct or indirect, in the regulation of p70^zap and its function in TcR/CD3 signaling.