Cross-talk between glycoprotein Ib and the collagen receptor GPVI in human platelets

固定化的血管性血友病因子（vonWillebrand factor，VWF）与血小板膜糖蛋白（GP）Ib -IX/V复合物之间的相互作用在血小板停滞和随后的血栓形成中是重要的。VWF与GPIb-IX/V复合物的结合引发了许多导致血小板活化的细胞内信号传导事件。我们最近的研究表明，VWF-肉毒素的相互作用以与胶原蛋白受体GPVI类似的方式介导血小板活化信号，即通过Fc受体γ链Syk和磷脂酶C γ2（PLCγ2）的酪氨酸磷酸化。我们发现，GPIb形成了一个复杂的Src和PI 3-激酶在静息血小板，GPIb相关的Src的量增加，响应VWF和肉毒素。PI 3激酶抑制剂wortmannin和Ly 294002对VWF介导的血小板聚集以及Src激活和FcRγ链的酪氨酸磷酸化没有影响。在这项研究中，我们还发现，GPIb的一部分组成与GPVI，其中他们已被定位在部分糖脂富集膜结构域（GEM）。在这里，我们提供了几条线的证据表明，GPIb介导的信号通路与GPVI相互作用，这两个受体之间的相互作用是依赖于GEM组织的信号在人类血小板。

The interaction between immobilized von Willebrand factor (VWF) and the platelet membrane glycoprotein (GP) Ib -IX/V complex is important in platelet arrest and subsequent thrombus formation. Binding of VWF to the GPIb-IX/V complex initiates a number of intracellular signaling events that lead to platelet activation. Our recent studies revealed that the interaction by VWF-botrocetin mediates platelet activation signals in a manner similar to that of the collagen receptor, GPVI, namely through tyrosine phosphorylation of the Fc receptor γ-chain, Syk and phospholipase C γ2 (PLCγ2). We found that GPIb formed a complex with Src and PI3-kinase in resting platelets, and the amount of GPIb-associated Src increased in response to VWF and botrocetin. PI3-kinase inhibitors, wortmannin and Ly294002 had no effects on VWF-mediated platelet aggregation, as well as Src activation and tyrosine phosphorylation of the FcRγ-chain. In this study, we have also found that a portion of GPIb constitutively associates with GPVI, where they have been localized in part to glycolipid-enriched membrane domains (GEMs). Here we provide several lines of evidence that GPIb-mediated signaling pathways interacts with GPVI, and that the interaction between these two receptors is dependent on GEM-organized signaling in human platelets.