McNicol A, Gerrard J M
Department of Oral Biology, Faculty of Dentistry, Winnipeg, Manitoba, Canada.
Blood Coagul Fibrinolysis. 1993 Dec;4(6):975-91.
Thrombin is by far the most potent platelet agonist. Potentially this reflects multiple intracellular processes involved in transmitting the activation signal from the initial contact with a receptor, or binding site, to the final platelet response. Platelet membranes have two putative receptors: the high affinity glycoprotein Ib, whose function remains to be clarified, and the moderate affinity autoproteolytic receptor. The autoproteolytic receptor is a member of a family of receptors, with seven transmembrane domains, which interact with GTP-binding proteins. Distal to the membrane, several forms of phospholipase C are activated and roles for both heterotrimeric and low molecular mass GTP-binding proteins have been presented. Phospholipase C acts on inositol phospholipids to generate inositol trisphosphate and diacylglycerol, both of which function as second messengers in thrombin-induced platelet activation. Inositol trisphosphate mobilizes internal calcium stores and this is accompanied, and enhanced, by an influx of calcium from the external milieu. Diacylglycerol and calcium both serve to regulate the activity of multiple protein kinases which, in turn, mediate the phosphorylated state of numerous proteins. Phosphorylation can occur on serine, threonine or tyrosine residues of target proteins and the phosphorylated state of these proteins determines the final activation of the platelet.
凝血酶是迄今为止最有效的血小板激动剂。这可能反映了从与受体或结合位点的初始接触到最终血小板反应传递激活信号所涉及的多个细胞内过程。血小板膜有两种假定的受体：高亲和力糖蛋白Ib，其功能尚待阐明，以及中等亲和力的自蛋白水解受体。自蛋白水解受体是一类受体的成员，具有七个跨膜结构域，与GTP结合蛋白相互作用。在膜的远端，几种形式的磷脂酶C被激活，并且已经提出了异三聚体和低分子量GTP结合蛋白的作用。磷脂酶C作用于肌醇磷脂以产生肌醇三磷酸和二酰基甘油，这两者在凝血酶诱导的血小板激活中均作为第二信使起作用。肌醇三磷酸动员细胞内钙储存，并且伴随着细胞外环境中钙的流入并增强了这种作用。二酰基甘油和钙都用于调节多种蛋白激酶的活性，这些蛋白激酶又介导许多蛋白质的磷酸化状态。磷酸化可以发生在靶蛋白的丝氨酸、苏氨酸或酪氨酸残基上，这些蛋白的磷酸化状态决定了血小板的最终激活。
