Bennett J S, Berger B W, Billings P C
Hematology-Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1:200-5. doi: 10.1111/j.1538-7836.2009.03378.x.
Integrins are a ubiquitous family of non-covalently associated alpha/beta transmembrane heterodimers linking extracellular ligands to intracellular signaling pathways [1] [Cell, 2002; 110: 673]. Platelets contain five integrins, three beta1 integrins that mediate platelet adhesion to the matrix proteins collagen, fibronectin and laminin, and the beta3 integrins alphavbeta3 and alphaIIbbeta3 [2] [J Clin Invest, 2005; 115: 3363]. While there are only several hundred alphavbeta3 molecules per platelet, alphavbeta3 mediates platelet adhesion to osteopontin and vitronectin in vitro [3] [J Biol Chem, 1997; 272: 8137]; whether this occurs in vivo remains unknown. By contrast, the 80,000 alphaIIbbeta3 molecules on agonist-stimulated platelets bind fibrinogen, von Willebrand factor, and fibronectin, mediating platelet aggregation when the bound proteins crosslink adjacent platelets [2] [J Clin Invest, 2005; 115: 3363]. Although platelet integrins are poised to shift from resting to active conformations, tight regulation of their activity is essential to prevent the formation of intravascular thrombi. This review focuses on the structure and function of the intensively studied beta3 integrins, in particular alphaIIbbeta3, but reference will be made to other integrins where relevant.
整合素是一类普遍存在的非共价结合的α/β跨膜异二聚体家族，它将细胞外配体与细胞内信号通路相连[1][《细胞》，2002年；110:673]。血小板含有五种整合素，三种β1整合素介导血小板与基质蛋白胶原蛋白、纤连蛋白和层粘连蛋白的黏附，以及β3整合素αvβ3和αIIbβ3[2][《临床研究杂志》，2005年；115:3363]。虽然每个血小板中只有几百个αvβ3分子，但αvβ3在体外介导血小板与骨桥蛋白和玻连蛋白的黏附[3][《生物化学杂志》，1997年；272:8137]；这种情况在体内是否发生仍不清楚。相比之下，激动剂刺激的血小板上的80,000个αIIbβ3分子结合纤维蛋白原、血管性血友病因子和纤连蛋白，当结合的蛋白质交联相邻血小板时介导血小板聚集[2][《临床研究杂志》，2005年；115:3363]。虽然血小板整合素随时准备从静息构象转变为活性构象，但对其活性进行严格调控对于防止血管内血栓形成至关重要。本综述重点关注深入研究的β3整合素，特别是αIIbβ3的结构和功能，但在相关情况下也会提及其他整合素。
