Russo Angela, Soh Unice J K, Trejo JoAnn
Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
Mol Interv. 2009 Apr;9(2):87-96. doi: 10.1124/mi.9.2.8.
Protease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that transmit cellular responses begun by the actions of extracellular proteases. The activation of a PAR occurs by a unique mechanism whereby the extracellular N-terminal segment of the inactive receptor undergoes proteolytic cleavage, resulting in irreversible activation--unlike most GPCRs that are reversibly activated. PARs mediate cellular responses to coagulant proteases in various cell types localized within the vasculature. Additionally, PARs are expressed in other cell types and respond to a plethora of proteases. Recent studies have revealed that different proteases elicit distinct responses through the activation of the same PAR. This phenomenon appears to involve stabilization of distinct active PAR conformations that facilitates selectively coupling to different effectors and is localized to caveolae, a subtype of lipid rafts.
蛋白酶激活受体（PARs）是G蛋白偶联受体（GPCRs），可传递由细胞外蛋白酶作用引发的细胞反应。PAR的激活通过一种独特的机制发生，即无活性受体的细胞外N端片段经历蛋白水解切割，导致不可逆激活——这与大多数可逆激活的GPCR不同。PARs介导血管系统内各种细胞类型对凝血蛋白酶的细胞反应。此外，PARs在其他细胞类型中表达，并对多种蛋白酶产生反应。最近的研究表明，不同的蛋白酶通过激活相同的PAR引发不同的反应。这种现象似乎涉及不同活性PAR构象的稳定，这有助于选择性地与不同效应器偶联，并定位于脂筏的一种亚型——小窝。
