THE FC-GAMMA-RII RECEPTOR TRIGGERS PP125(FAK) PHOSPHORYLATION IN PLATELETS

Platelets express a single low affinity receptor for immunoglobulin, F c gamma RII, that triggers multiple cellular responses upon interactio n with multivalent immune complexes, In this study we show that immobi lized IBG is also a potent stimulant of platelet activation triggering adhesion, aggregation, massive dense granule secretion, and thromboxa ne production, Platelet adhesion to IgG was blocked by the Fc gamma RI I receptor-specific monoclonal antibody, IV.3. Pretreatment of the pla telets with cytochalasin D to inhibit actin polymerization similarly p revented cell binding to IgQ having no effect on platelet binding to f ibrinogen. Platelet adhesion to IgG also led to the induction of tyros ine phosphorylation of multiple proteins including pp125(FAK) and p72( SYK). These proteins were also tyrosine-phosphorylated in alpha(IIb)be ta(3)-deficient IgG-adherent platelets from patients with Glanzmann's thrombasthenia. These data demonstrate that Fc gamma RII mediates pp12 5(FAK) phosphorylation and platelet adhesion to IgG independent of the integrin alpha(IIb)beta(3). Treatment of the platelets with bisindoly lmaleimide to inhibit protein kinase C prevented phosphorylation of pp 125(FAK) as well as several other proteins, but not p72(SYK) phosphory lation. This study establishes that the Fc gamma RII receptor mediates pp125(FAK) phosphorylation via protein kinase C.