Role of Fc receptor gamma-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 botroc etin, by interacting with GPlb, induced tyrosine phosphorylation of Fc rece ptor 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 an d Syk, suggesting that Src and Lyn are involved in FcR gamma -chain tyrosin e phosphorylation and downstream signals. In spite of the PLC gamma2 tyrosi ne phosphorylation, however, there was no intracellular calcium release and inositol 1,4,5-trisphosphate production. In Brij 35 lysates, FcR gamma -ch ain was found to constitutively associate with GPlb, The number of GPlb exp ressed on FcR gamma -chain-deficient platelets was comparable to that of th e wild-type, as assessed by flow cytometry, However, tyrosine phosphorylati on of Syk, LAT, and PLC gammaP in response to vWF plus botrocetin was signi ficantly suppressed, suggesting that FcR gamma -chain mediates activation s ignals 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 f or the full activation of platelets mediated by GPlb.