DIFFERENTIAL ACTIVATION OF THE TYROSINE KINASES ZAP-70 AND SYK AFTER FC-GAMMA-RI STIMULATION

Engagement of the high-affinity IgG Fc receptor (Fc gamma RI) activate s a signal transduction pathway involving tyrosine phosphorylation of associated kinases. We compared the activation of the related protein tyrosine kinases (PTKs), Syk and ZAP-70, in Fc gamma RI-mediated signa ling. Cross-linking of the Fc gamma RI multimeric receptor in monocyti c cells results in tyrosine phosphorylation of the Fc epsilon RI gamma subunit and association of Syk with this complex. We stably introduce d ZAP-70 via a retroviral vector into two monocytic cell lines, U937 a nd THP-1. which normally do not express ZAP-70. Neither Syk nor MAP ki nase activation was affected by the presence of ZAP-70. Although trans duced ZAP-70 had in vitro kinase activity and associated with Fc epsil on RI gamma after receptor aggregation, it was not tyrosine phosphoryl ated. In contrast, both ZAP-TIG and Syk were phosphorylated in a T-cel l line in which their respective levels of expression were similar to those detected in U937/ZAP-70 cells. Therefore, these results suggest that requirements for Syk and ZAP-70 phosphorylation are distinct in a monocytic cell context. (C) 1997 by The American Society of Hematolog y.