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

人血小板中糖蛋白 Ib 和胶原蛋白受体 GPVI 之间的串扰

基本信息

批准号：
13671056
负责人：
ASAZUMA Naoki
金额：
$ 1.92万
依托单位：
Faculty of Medicine, University of Yamanashi
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671056/
关键词：
Platelet glycoprotein Ib glycoprotein VI von Willebrand factor tyrosine kinase Src family kinase PI3-kinase von Willebrand Factor tyrosin kinase

项目摘要

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.

固定化血管性血友病因子（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骤停和随后的血栓形成中很重要。VWF与GPIb-IX/V复合物的结合启动了许多导致血小板活化的细胞内信号事件。我们最近的研究表明，VWF-botrocetin的相互作用以类似于胶原受体GPVI的方式介导血小板激活信号，即通过酪氨酸磷酸化Fc受体γ链，Syk和磷脂酶Cγ2 （PLCγ2）。我们发现GPIb在静息血小板中与Src和pi3激酶形成复合物，并且GPIb相关Src的数量在VWF和botrocetin的反应中增加。pi3激酶抑制剂、wortmannin和Ly294002对vwf介导的血小板聚集、Src激活和fcr γ链酪氨酸磷酸化均无影响。在这项研究中，我们还发现GPIb的一部分组成性地与GPVI结合，其中它们部分定位于糖脂富集膜结构域（GEMs）。在这里，我们提供了几条证据，证明gpib介导的信号通路与GPVI相互作用，并且这两个受体之间的相互作用依赖于人类血小板中gem组织的信号传导。