Analysis of signal transduction pathways through glycoprotein Ib in human platelets.

人血小板中通过糖蛋白 Ib 的信号转导途径分析。

基本信息

批准号：
11672294
负责人：
SATOH Kaneo
金额：
$ 2.18万
依托单位：
Yamanashi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672294/
关键词：
platelet glycoprotein Ib von Willebrand factor snake venom platelet aggregation tyrosine kinase

项目摘要

In vivo platelet adhesion to the damaged vessel wall and subsequent platelet-platelet interaction is essential for hemostasis and thrombogenesis. The most initial step involved in this process is the interaction between the glycoprotein Ib (GPIb) and von Willebrand factor (vWF).A number of snake venoms (botrocetin, alboaggregin-B, echicetin, Jararaca GPIb-BP, flavocetin-A) have been identified that affect the interaction between vWF and GPIb. They have proved to be valuable tools for elucidating the biological mechanism underling the GPIb-related platelet activation. In this study, we compared the effects of these GPIb-binding proteins on various parameters of platelet activation. Association of GPIb and Src, tyrosine phosphorylation of 64kDa protein, and platelet aggregation were induced by alboaggregin-B and flavocetin-A.In addition to those reactions, redistribution of Src, Lyn, and 14-3-3 to cytoskeletons and Ca^<++> influx were induced by botrocetin in the presence of vWF.However, botrocetin, in the presence of monomeric vWF, could not induced platelet aggregation, Ca^<2+> influx, and cytoskeletal association of tyrosine kinases. Echicetin or Jararaca GPIb-BP caused no reaction in these parameters.These results suggested that tyrosine kinase might be strongly related in GPIb signal transduction(s). Since botrocetin could not induce platelet activation in the presence of monomeric vWF, the activation of platelets appear to require the clustering of GPIb by the vWF molecules with multiple binding sites.

体内血小板粘附在受损的血管壁上，随后的血小板 - 血小板相互作用对于止血和血栓形成至关重要。此过程中涉及的最初的一步是糖蛋白IB（GPIB）和Von Willebrand因子（VWF）之间的相互作用。蛇毒（Botrocetin，Alboaggregin-b，echicetin，echicetin，echicetin，echicetin，jararaca gpib bp，gpib-bp，gpib-bp，gpib-bp，flavocetin-a）已经鉴定出了互动之间的互动。事实证明，它们是阐明与GPIB相关血小板激活下的生物学机制的宝贵工具。在这项研究中，我们比较了这些GPIB结合蛋白对血小板激活的各种参数的影响。 GPIB和SRC的关联，64KDA蛋白的酪氨酸磷酸化和血小板聚集的相关性通过Alboaggregin-B和黄昔蛋白-A.A诱导，在这些反应，Src，Lyn的再分配和ca^<++> usbr.ever theefr.ever中的src，lyn和14-3-3的相关性。在存在单体VWF的情况下，botrocetin无法诱导血小板聚集，Ca^<2+>流入和酪氨酸激酶的细胞骨架缔合。 echicetin或jararaca gpib-bp在这些参数中没有引起任何反应。这些结果表明，酪氨酸激酶在GPIB信号转导（S）中可能密切相关。由于在存在单体VWF的情况下，溴环蛋白无法诱导血小板激活，因此血小板的激活似乎需要具有多个结合位点的VWF分子聚集GPIB。