Signaling and regulation of the platelet glycoprotein Ib-IX-V complex
Signaling and regulation of the platelet glycoprotein Ib-IX-V complex
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DOI：
10.1097/moh.0b013e3280dce51a
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发表时间：
2007-05-01
影响因子：
3.2
通讯作者：
Du, Xiaoping
中科院分区：
文献类型：
--
作者：
Du, Xiaoping
血小板粘附受体糖蛋白Ib-IX-V复合物不仅介导血小板粘附，而且传递导致血小板活化、聚集和分泌的信号。近年来，有关糖蛋白Ib-IX-V功能的信号通路和调控机制的研究取得了重大进展。糖蛋白Ib-IX-V与其配体von Willebrand因子的相互作用受到von Willebrand因子构象和细胞内信号介导的糖蛋白Ib-IX-V受体功能调节的双重控制，这需要14-3-3蛋白家族的异构体（14-3-3 zeta）。糖蛋白Ib-IX-V信号通路由Src家族蛋白激酶、磷脂酶C、钙升高、磷酸肌醇3-激酶以及多种扩增机制介导，包括一氧化氮- cgmp途径、丝裂原激活的蛋白激酶途径、基于免疫受体酪氨酸的激活基元途径、ADP和血栓素A(2)途径。对糖蛋白Ib-IX-V调节机制的了解将有助于开发干扰或增强其血管性血友病因子结合功能的抑制剂和调节剂，从而有助于治疗血栓和出血性疾病。糖蛋白Ib-IX-V信号传导的细胞内分子和途径的表征对新药物的开发和影响糖蛋白Ib-IX-V信号传导的现有药物的使用具有重要意义。
Purpose of review The platelet adhesion receptor, the glycoprotein Ib-IX-V complex, not only mediates platelet adhesion but also transmits signals leading to platelet activation, aggregation and secretion. Significant progress has been made recently on the signaling pathways and regulatory mechanisms involving glycoprotein Ib-IX-V function.Recent findings The interaction of glycoprotein Ib-IX-V with its ligand, von Willebrand factor, is dually controlled by von Willebrand factor conformation and intracellular signal-mediated regulation of glycoprotein Ib-IX-V receptor function that requires the isoform of the 14-3-3 protein family (14-3-3 zeta). Glycoprotein Ib-IX-V signaling is mediated by the Src family of protein kinases, phospholipase C, calcium elevation, phosphoinositol 3-kinase, and multiple amplification mechanisms including the nitric oxide-cGMP pathway, the mitogen-activated protein kinase pathway, the immunoreceptor tyrosine-based activation motif pathway, and ADP and thromboxane A(2) pathways.Summary Progress in understanding the mechanism(s) regulating glycoprotein Ib-IX-V should help develop inhibitors and modifiers that interfere or augment its von Willebrand factor binding function and thus be useful for treating thrombosis and bleeding disorders. Characterization of intracellular molecules and pathways in glycoprotein Ib-IX-V signaling ha s implications in the development of new agents and for the use of existing drugs that affect glycoprotein Ib-IX-V signaling.