Thrombin receptor structure and function.
Thrombin receptor structure and function.
复制标题
凝血酶受体的结构和功能。
DOI：
10.1101/sqb.1992.057.01.019
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Hung,DT
中科院分区：
文献类型：
--
作者：
Coughlin,SR;Scarborough,RM;Vu,TK;Hung,DT
与细胞表面相互作用的蛋白酶如何引起细胞内信号传导事件？本文综述的功能性凝血酶受体的最新克隆和表征提供了这个问题的一个答案（Liu 等人，1991；Rasmussen 等人，1991；Vu 等人，1991a, b；Coughlin 等人，1992；Hung 等人，1992a, b, c, d；Scarborough 等人，1992）。凝血酶是一种在血管损伤部位产生的多功能丝氨酸蛋白酶。它对可溶性蛋白质底物和细胞的不同作用可以被视为不仅协调止血反应，而且还可能协调对受伤的炎症和增殖反应。除了将纤维蛋白原裂解为纤维蛋白单体以形成血栓的纤维网之外，凝血酶还是多种细胞类型的有效激活剂。首先，凝血酶是最有效的血小板聚集刺激剂（Davey 和 Luscher，1967 年；S human，1986 年），凝血酶活性可能对体内动脉血栓形成至关重要（Hanson 和 Harker，1988 年；Eidt 等人，1989 年；Fitzgerald 和 Fitzgerald，1989 年；Heras 等人，1989 年；Jang 等人，1989 年）。 1989）。凝血酶对其他细胞类型的多种作用主要是在体外确定的。凝血酶对单核细胞具有趋化性（Bar-Shavit et al. 1983），对淋巴细胞和间充质细胞（包括血管平滑肌细胞）具有促有丝分裂作用（Chen and Buchanan 1975；Chen et al. 1976；McNamara et al. 1992），并且它对血管内皮有多种影响。这些包括刺激内皮产生前列环素（Weksler et al. 1978）、血小板激活因子（Prescott et al. 1984）、纤溶酶原激活剂抑制剂（Gelehrter and Sznycer-Laszyk 1986）和强效平滑肌细胞有丝分裂原血小板衍生生长因子（Daniel et al. 1986），凝血酶还诱导中性粒细胞粘附在血管壁上（Zimmerman 等人，1986），可能是通过刺激内皮表面 P-选择素的表达（Hattori 等人，1989）。凝血酶的这些不同作用是否是体内炎症和增殖反应的重要介质仍有待确定。负责血小板和其他细胞的凝血酶激活的受体的鉴定有可能提供解决此类问题的试剂，并为抗血栓治疗和可能的抗增殖或抗炎治疗提供新靶标。凝血酶激活血小板和其他细胞的可能机制的理论包括经典的受体占据、受体的蛋白水解裂解及其组合（Berndt 等，1985；
How do proteases that interact with the cell surface cause intracellular signaling events? One answer to this question was provided by the recent cloning and characterization of a functional thrombin receptor reviewed herein (Liu et al. 1991; Rasmussen et al. 1991; Vu et al. 1991a, b; Coughlin et al. 1992; Hung et al. 1992a, b, c, d; Scarborough et al. 1992). Thrombin is a multifunctional serine protease generated at sites of vascular injury. Its varied actions on both soluble protein substrates and cells may be viewed as orchestrating not only hemostatic responses, but also perhaps inflammatory and proliferative responses to wounding. In addition to cleaving fibrinogen to the fibrin monomer to form the fibrous meshwork of blood clots, thrornbin is a potent activator of a number of cell types. First and foremost, thrombin is the most potent stimulator of platelet aggregation (Davey and Luscher 1967; Shuman 1986), a thrombin activity probably critical in arterial thrombosis in vivo (Hanson and Harker 1988; Eidt et al. 1989; Fitzgerald and Fitzgerald 1989; Heras et al. 1989; Jang et al. 1989). A variety of thrombin actions on other cells types have been defined largely in vitro. Thrombin is chemotactic for monocytes (Bar-Shavit et al. 1983) and mitogenic for lymphocytes and for mesenchymal cells, including vascular smooth muscle cells (Chen and Buchanan 1975; Chen et al. 1976; McNamara et al. 1992), and it has a number of effects on the vascular endothelium. These include stimulating endothelial production of prostacyclin (Weksler et al. 1978), platelet-activating factor (Prescott et al. 1984), plasminogen activator-inhibitor (Gelehrter and Sznycer-Laszyk 1986), and the potent smooth muscle cell mitogen platelet-derived growth factor (Daniel et al. 1986), Thrombin also induces neutrophil adherence to the vessel wall (Zimmerman et al. 1986), probably by stimulating the expression of P-selectin on the endothelial surface (Hattori et al. 1989). Whether these disparate actions of thrombin are important mediators of inflammatory and proliferative responses in vivo remains to be defined. Identification of the receptor responsible for thrombin activation of platelets and other cells held the possibility of providing reagents for addressing such issues and of providing a new target for antithrombotic therapy and possibly antiproliferative or anti-inflammatory therapies. Theories of possible mechanisms by which thrombin might activate platelets and other cells have included classical receptor occupancy, proteolytic cleavage of a receptor, and combinations thereof (Berndt et al. 1985;