Role of Fc receptor γ-chain in platelet glycoprotein Ib–mediated signaling
Copyright policy )Role of Fc receptor γ-chain in platelet glycoprotein Ib–mediated signaling
Interaction between von Willebrand factor (vWF) and glycoprotein Ib (GPIb) stimulates tyrosine kinases and subsequent tyrosine phosphorylation events in human platelets. This study found that the combination of vWF and botrocetin, by interacting with GPIb, induced tyrosine phosphorylation of Fc receptor γ-chain (FcR γ-chain), Syk, linker for activation of T cells (LAT), and phospholipase C γ2 (PLCγ2). Pretreatment of platelets with 10 μM PP1 completely inhibited these tyrosine phosphorylation events. On GPIb stimulation, Src and Lyn formed a complex with FcR γ-chain and Syk, suggesting that Src and Lyn are involved in FcR γ-chain tyrosine phosphorylation and downstream signals. In spite of the PLCγ2 tyrosine phosphorylation, however, there was no intracellular calcium release and inositol 1,4,5-trisphosphate production. In Brij 35 lysates, FcR γ-chain was found to constitutively associate with GPIb. The number of GPIb expressed on FcR γ-chain–deficient platelets was comparable to that of the wild-type, as assessed by flow cytometry. However, tyrosine phosphorylation of Syk, LAT, and PLCγ2 in response to vWF plus botrocetin was significantly suppressed, suggesting that FcR γ-chain mediates activation signals related to GPIb. Compared with the aggregation response of wild-type platelets, that of FcR γ-chain–deficient platelets in response to vWF plus botrocetin was impaired, implying that FcR γ-chain is required for the full activation of platelets mediated by GPIb.
- University of Yamanashi Japan
Blood Platelets, Enzyme Precursors, Platelet Aggregation, Phospholipase C gamma, Amino Acid Motifs, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Platelet Membrane Glycoproteins, Phosphoproteins, Mice, Mutant Strains, Isoenzymes, Mice, Inbred C57BL, Mice, Platelet Glycoprotein GPIb-IX Complex, Animals, Humans, Phosphorylation, Carrier Proteins, Adaptor Proteins, Signal Transducing, Protein Binding
Blood Platelets, Enzyme Precursors, Platelet Aggregation, Phospholipase C gamma, Amino Acid Motifs, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Platelet Membrane Glycoproteins, Phosphoproteins, Mice, Mutant Strains, Isoenzymes, Mice, Inbred C57BL, Mice, Platelet Glycoprotein GPIb-IX Complex, Animals, Humans, Phosphorylation, Carrier Proteins, Adaptor Proteins, Signal Transducing, Protein Binding
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