IGA FC RECEPTOR (CD89) ACTIVATION ENABLES COUPLING TO SYK AND BTK TYROSINE KINASE PATHWAYS - DIFFERENTIAL SIGNALING AFTER IFN-GAMMA OR PHORBOL ESTER STIMULATION

IgA Fc receptors (Fc alpha R) can mediate a variety of inflammatory re sponses. It has been demonstrated that the FcR gamma subunit is critic al in mediating signaling through Fc alpha R. We show that aggregation of Fc alpha R on U937 cells and blood neutrophils results in tyrosine phosphorylation of several intracellular proteins, including the FcR gamma subunit, p72(syk), and Bruton tyrosine kinase (Btk). Syk was fou nd to be associated with Fc alpha R and its phosphorylation was increa sed in phorbol myristate acetate (PMA)- and interferon-gamma (IFN-gamm a)-treated U937 cells. In contrast, phosphorylation of Btk was only de tected after cell treatment with PMA but not IFN-gamma. Those data ind icate that signaling through Fc alpha R gamma(2) involves at least two subfamilies of tyrosine kinases, syk and Btk. Our results also sugges t that activation of tyrosine kinase pathways through Fc alpha R depen ds on the activation state of the cell. This may be an important regul atory mechanism in IgA-mediated responses at inflammatory sites.