Ishihara H, Connolly A J, Zeng D, Kahn M L, Zheng Y W, Timmons C, Tram T, Coughlin S R
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Nature. 1997 Apr 3;386(6624):502-6. doi: 10.1038/386502a0.
Thrombin is a coagulation protease that activates platelets, leukocytes, endothelial and mesenchymal cells at sites of vascular injury, acting partly through an unusual proteolytically activated G-protein-coupled receptor. Knockout of the gene encoding this receptor provided definitive evidence for a second thrombin receptor in mouse platelets and for tissue-specific roles for different thrombin receptors. We now report the cloning and characterization of a new human thrombin receptor, designated protease-activated receptor 3 (PAR3). PAR3 can mediate thrombin-triggered phosphoinositide hydrolysis and is expressed in a variety of tissues, including human bone marrow and mouse megakaryocytes, making it a candidate for the sought-after second platelet thrombin receptor. PAR3 provides a new tool for understanding thrombin signalling and a possible target for therapeutics designed selectively to block thrombotic, inflammatory and proliferative responses to thrombin.
凝血酶是一种凝血蛋白酶，可在血管损伤部位激活血小板、白细胞、内皮细胞和间充质细胞，部分通过一种异常的蛋白水解激活的G蛋白偶联受体发挥作用。编码该受体的基因敲除为小鼠血小板中第二种凝血酶受体以及不同凝血酶受体的组织特异性作用提供了确凿证据。我们现在报告一种新的人类凝血酶受体的克隆和特性，命名为蛋白酶激活受体3（PAR3）。PAR3可介导凝血酶触发的磷酸肌醇水解，并在多种组织中表达，包括人类骨髓和小鼠巨核细胞，使其成为寻找的第二种血小板凝血酶受体的候选者。PAR3为理解凝血酶信号传导提供了一种新工具，也是设计用于选择性阻断对凝血酶的血栓形成、炎症和增殖反应的治疗方法可能的靶点。
