Progress in the understanding of protease-activated receptors
Progress in the understanding of protease-activated receptors
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DOI：
10.1532/ijh97.03165
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发表时间：
2004-02-01
影响因子：
2.1
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Gabazza, EC;Taguchi, O;Suzuki, K
凝血酶是凝血系统激活的产物。它是一种多功能蛋白质，除了止血和血栓形成功能外，还具有将凝血系统与炎症反应联系起来的几种细胞效应。许多年的研究是必要的第一个功能性凝血酶受体的发现，它被发现有一个独特的激活机制。该受体被命名为蛋白酶激活受体1（PAR-1），因为蛋白水解是其激活所必需的。随后的研究鉴定了其他PAR，PAR-2，PAR-3和PAR-4。PAR-2可被胰蛋白酶、类胰蛋白酶、因子Xa或因子VIIa激活，但不能被凝血酶激活。PAR-3和PAR-4也可以被凝血酶激活。通过蛋白酶激活PAR涉及蛋白水解切割和氨基末端受体序列的解蔽，所述氨基末端受体序列通过与受体的第二胞外环结合以启动跨膜信号传导而充当栓系配体。序列分析表明，所有PAR都是7-跨膜结构域受体超家族的成员。PAR的表达已在大多数组织和许多细胞中检测到，因此这些分子与几种生理过程和几种疾病的发病机制有关。
Thrombin results from the activation of the blood coagulation system. It is a multifunctional protein that has, besides its function in hemostasis and thrombosis, several cellular effects that link the coagulation system with the inflammatory response. Many years of investigations were necessary for the discovery of the first functional thrombin receptor, which was found to have a unique mechanism of activation. The receptor was named protease-activated receptor 1 (PAR-1) because proteolysis is necessary for its activation. Subsequent studies led to the identification of the other PARs, PAR-2, PAR-3, and PAR-4. PAR-2 is activated by trypsin, tryptase, factor Xa, or factor VIIa, but it cannot be activated by thrombin. PAR-3 and PAR-4 can also be activated by thrombin. Activation of PARs by protease involves proteolytic cleavage and unmasking of an amino-terminal receptor sequence, which acts as a tethered ligand by binding to the second extracellular loop of the receptor to initiate transmembrane signaling. Sequence analysis has shown that all PARs are members of the 7-transmembrane domain receptor superfamily. Expression of PARs has been detected in most tissues and in numerous cells, and thus these molecules have been implicated in several physiological processes and in the pathogenesis of several diseases.