The FcγRII Receptor Triggers pp125FAK Phosphorylation in Platelets

Abstract Platelets express a single low affinity receptor for immunoglobulin, FcγRII, that triggers multiple cellular responses upon interaction with multivalent immune complexes. In this study we show that immobilized IgG is also a potent stimulant of platelet activation triggering adhesion, aggregation, massive dense granule secretion, and thromboxane production. Platelet adhesion to IgG was blocked by the FcγRII receptor-specific monoclonal antibody, IV.3. Pretreatment of the platelets with cytochalasin D to inhibit actin polymerization similarly prevented cell binding to IgG having no effect on platelet binding to fibrinogen. Platelet adhesion to IgG also led to the induction of tyrosine phosphorylation of multiple proteins including pp125FAK and p72SYK. These proteins were also tyrosine-phosphorylated in αIIbβ3-deficient IgG-adherent platelets from patients with Glanzmann's thrombasthenia. These data demonstrate that FcγRII mediates pp125FAK phosphorylation and platelet adhesion to IgG independent of the integrin αIIbβ3. Treatment of the platelets with bisindolylmaleimide to inhibit protein kinase C prevented phosphorylation of pp125FAK as well as several other proteins, but not p72SYK phosphorylation. This study establishes that the FcγRII receptor mediates pp125FAK phosphorylation via protein kinase C.