Cupit L D, Schmidt V A, Bahou W F
Department of Medicine, State University of New York at Stony Brook 11794-8151, USA.
Trends Cardiovasc Med. 1999 Jan-Feb;9(1-2):42-8. doi: 10.1016/s1050-1738(99)00005-5.
Macromolecular assembly and generation of serine proteases on cellular surfaces is critically involved in regulation of hemostatic, inflammatory, or fibrinolytic pathways. The concept that a number of these serine proteases may effect cellular activation and proliferative responses has engendered an emerging paradigm focusing on the molecular mechanisms regulating cellular/protease interactions. Previous data suggest that some of these cellular responses are mediated by a novel class of G protein-coupled proteolytically activated receptors. Proteolytically activated receptor-3 (PAR-3) is the third member of this rapidly emerging gene family, all three of which (PAR-1, PAR-2, PAR-3) are known to co-cluster in the human genome, and are expressed on vascular endothelial cells, cells which critically regulate the hemostatic repertoire. This review will focus on the genetics of these receptors (emphasizing recent advances in the identification and characterization of PAR-3), review known structure/function similarities, and outline potential links in regulation of the hemostatic response by protease generation on the endothelial cell surface.
大分子组装以及丝氨酸蛋白酶在细胞表面的生成，在止血、炎症或纤维蛋白溶解途径的调节中起着关键作用。许多这类丝氨酸蛋白酶可能影响细胞活化和增殖反应的这一概念，催生了一种新兴的范式，其聚焦于调节细胞/蛋白酶相互作用的分子机制。先前的数据表明，其中一些细胞反应是由一类新型的G蛋白偶联蛋白水解激活受体介导的。蛋白水解激活受体-3（PAR-3）是这个迅速兴起的基因家族的第三个成员，已知这三个成员（PAR-1、PAR-2、PAR-3）在人类基因组中共同聚类，并在血管内皮细胞上表达，而血管内皮细胞对止血功能起着关键的调节作用。本综述将聚焦于这些受体的遗传学（重点介绍PAR-3鉴定和表征方面的最新进展），回顾已知的结构/功能相似性，并概述内皮细胞表面蛋白酶生成对止血反应调节的潜在联系。
