Brass L F, Hoxie J A, Manning D R
Department of Medicine, University of Pennsylvania, Philadelphia.
Thromb Haemost. 1993 Jul 1;70(1):217-23.
Recent studies have helped to define the early events of signal transduction in platelets. The best-described of these events are those in which heterotrimeric guanine nucleotide binding regulatory proteins (G proteins) mediate the interaction between cell surface receptors for agonists and intracellular second messenger generating enzymes. To date nine different G proteins have been identified in platelets. Their targets include phospholipases C and A2, and adenylyl cyclase. Efforts to clone the receptors that can couple to these G proteins have been successful for epinephrine, thrombin, TxA2 and platelet activating factor. Each of these is comprised of a single polypeptide with seven transmembrane domains and an extracellular N-terminus. In the case of the thrombin receptor, activation occurs by a novel mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Shortly after activation, thrombin receptors become resistant to re-activation by thrombin. This desensitization, which appears to involve receptor phosphorylation and internalization, provides a potent mechanism for limiting the duration of thrombin-initiated events in platelets and other thrombin-responsive vascular cells.
最近的研究有助于明确血小板信号转导的早期事件。其中描述得最为详尽的事件是那些异三聚体鸟嘌呤核苷酸结合调节蛋白（G蛋白）介导激动剂的细胞表面受体与细胞内第二信使生成酶之间相互作用的事件。迄今为止，已在血小板中鉴定出九种不同的G蛋白。它们的作用靶点包括磷脂酶C和A2以及腺苷酸环化酶。对于肾上腺素、凝血酶、血栓素A2和血小板活化因子，克隆能够与这些G蛋白偶联的受体的工作已取得成功。这些受体均由具有七个跨膜结构域和一个细胞外N端的单一多肽组成。就凝血酶受体而言，其激活通过一种新机制发生，即凝血酶裂解其受体，产生一个可作为拴系配体的新N端。激活后不久，凝血酶受体就会对凝血酶的再次激活产生抗性。这种脱敏现象似乎涉及受体磷酸化和内化，为限制血小板及其他凝血酶反应性血管细胞中凝血酶引发事件的持续时间提供了一种有效机制。
