Biochemistry Unit, Faculty of Medical Sciences, University of the, West Indies, St. Augustine, Trinidad, West Indies.
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, 33101, USA.
Mol Cell Biochem. 2004 Aug;263(1):227-39. doi: 10.1023/B:MCBI.0000041864.14092.5b.
Recent studies have shown that a novel class of protease activated receptors (PARs), which are composed of seven transmembrane G protein-coupled domains, are activated by serine proteases such as thrombin, trypsin and tryptase. Although four types (PAR 1, PAR 2, PAR 3 and PAR 4) of this class of receptors have been identified, their discrete physiological and pathological roles are still being unraveled. Extracellular proteolytic activation of PARs results in the cleavage of specific sites in the extracellular domain and formation of a new N-terminus which functions as a tethered ligand. The newly formed tethered ligand binds intramolecularly to an exposed site in the second transmembrane loop and triggers G-protein binding and intracellular signaling. Recent studies have shown that PAR-1, PAR-2 and PAR-4 have been involved in vascular development and a variety of other biological processes including apoptosis and remodeling. The use of animal model systems, mainly transgenic mice and synthetic tethered ligand domains, have contributed enormously to our knowledge of molecular signaling and the regulatory properties of various PARs in cardiomyocytes. This review focuses on the role of PARs in cardiovascular function and disease. (Mol Cell Biochem 263: 227-239, 2004).
最近的研究表明，一类新型的蛋白酶激活受体（PARs）由七个跨膜 G 蛋白偶联结构域组成，可被凝血酶、胰蛋白酶和类胰蛋白酶等丝氨酸蛋白酶激活。虽然已经鉴定出该受体家族的四种类型（PAR1、PAR2、PAR3 和 PAR4），但其不同的生理和病理作用仍在逐步揭示中。PARs 的细胞外蛋白水解激活导致细胞外结构域中特定部位的切割和新 N 端的形成，后者作为连接配体发挥作用。新形成的连接配体在第二跨膜环内分子间结合，并触发 G 蛋白结合和细胞内信号转导。最近的研究表明，PAR-1、PAR-2 和 PAR-4 参与了血管发育和多种其他生物学过程，包括细胞凋亡和重塑。动物模型系统（主要是转基因小鼠和合成连接配体结构域）的应用极大地促进了我们对心肌细胞中各种 PAR 分子信号转导和调节特性的认识。本文综述了 PARs 在心血管功能和疾病中的作用。（Mol Cell Biochem 263: 227-239, 2004）。
