ACTIVATION OF PROTEIN-TYROSINE KINASE PYK2 IS DOWNSTREAM OF SYK IN FC-EPSILON-RI SIGNALING

Aggregation of the Fc epsilon RI, a member of the immune receptor fami ly, induces the activation of protein-tyrosine kinases and results in tyrosine phosphorylation of proteins that are involved in downstream s ignaling pathways. Here we report that Pyk2, another member of the foc al adhesion kinase family, was present in the RBL-2H3 mast cell line a nd was rapidly tyrosine-phosphorylated and activated after Fc epsilon RI aggregation. Tyrosine phosphorylation of Pyk2 was also induced by t he calcium ionophore A23187, by phorbol myristate acetate, or by stimu lation of G-protein-coupled receptors. Adherence of cells to fibronect in dramatically enhanced the induced tyrosine phosphorylation of Pyk2. Although Src family kinases are activated by Fc epsilon RI stimulatio n and tyrosine-phosphorylate the receptor subunits, the activation and tyrosine phosphorylation of Pyk2 were downstream of Syk. In contrast, tyrosine phosphorylation of Pyk2 by stimulation of G-protein-coupled receptors was independent of Syk. Therefore, the Fc epsilon RI-induced tyrosine phosphorylation of Pyk2 is downstream of Syk and may play a role in cell secretion.