Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Semin Immunopathol. 2012 Jan;34(1):133-49. doi: 10.1007/s00281-011-0289-1. Epub 2011 Oct 6.
Protease-activated receptors (PARs) are G protein-coupled receptors that are activated by proteolytical cleavage of the amino-terminus and thereby act as sensors for extracellular proteases. While coagulation proteases activate PARs to regulate hemostasis, thrombosis, and cardiovascular function, PAR2 is also activated in extravascular locations by a broad array of serine proteases, including trypsin, tissue kallikreins, coagulation factors VIIa and Xa, mast cell tryptase, and transmembrane serine proteases. Administration of PAR2-specific agonistic and antagonistic peptides, as well as studies in PAR2 knockout mice, identified critical functions of PAR2 in development, inflammation, immunity, and angiogenesis. Here, we review these roles of PAR2 with an emphasis on the role of coagulation and other extracellular protease pathways that cleave PAR2 in epithelial, immune, and neuronal cells to regulate physiological and pathophysiological processes.
蛋白酶激活受体 (PARs) 是 G 蛋白偶联受体，其氨基末端通过蛋白水解切割而被激活，从而作为细胞外蛋白酶的传感器。虽然凝血蛋白酶激活 PARs 以调节止血、血栓形成和心血管功能，但 PAR2 也被广泛的丝氨酸蛋白酶（包括胰蛋白酶、组织激肽释放酶、凝血因子 VIIa 和 Xa、肥大细胞胰蛋白酶和跨膜丝氨酸蛋白酶）在血管外位置激活。PAR2 特异性激动肽和拮抗肽的给药以及 PAR2 基因敲除小鼠的研究确定了 PAR2 在发育、炎症、免疫和血管生成中的关键功能。在这里，我们重点介绍了凝血和其他细胞外蛋白酶途径在调节上皮细胞、免疫细胞和神经元细胞中 PAR2 的生理和病理生理过程中的作用，综述了 PAR2 的这些作用。
