Role of Fc receptor γ-chain in platelet glycoprotein Ib-mediated signaling

Interaction between von Willebrand factor (VWF) and glycoprotein Ib (GPlb) stimulates tyrosine kinases and subsequent tyrosine phosphorylation events in human platelets. This study found that the combination of vWF and botrocetin, by interacting with GPlb, induced tyrosine phosphorylation of Fc receptor gamma -chain (FcR gamma -chain), Syk, linker for activation of T cells (LAT), and phospholipase C gamma2 (PLC gammaP), Pretreatment of platelets with 10 muM PP1 completely inhibited these tyrosine phosphorylation events. On GPlb stimulation, Src and Lyn formed a complex with FcR gamma -chain and Syk, suggesting that Src and Lyn are involved in FcR gamma -chain tyrosine phosphorylation and downstream signals. In spite of the PLC gamma2 tyrosine phosphorylation, however, there was no intracellular calcium release and inositol 1,4,5-trisphosphate production. In Brij 35 lysates, FcR gamma -chain was found to constitutively associate with GPlb, The number of GPlb expressed on FcR gamma -chain-deficient platelets was comparable to that of the wild-type, as assessed by flow cytometry, However, tyrosine phosphorylation of Syk, LAT, and PLC gammaP in response to vWF plus botrocetin was significantly suppressed, suggesting that FcR gamma -chain mediates activation signals related to GPlb, Compared with the aggregation response of wild-type platelets, that of FcR gamma -chain-deficient platelets in response to VWF plus botrocetin was impaired, implying that FcR gamma -chain is required for the full activation of platelets mediated by GPlb.