Gabazza Esteban C, Taguchi Osamu, Kamada Haruhito, Hayashi Tatsuya, Adachi Yukihiko, Suzuki Koji
Department of Molecular Pathobiology, Mie University School of Medicine, Tsu City, Mie, Japan.
Int J Hematol. 2004 Feb;79(2):117-22. doi: 10.1532/ijh97.03165.
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.
凝血酶由血液凝固系统激活产生。它是一种多功能蛋白质，除了在止血和血栓形成中发挥作用外，还具有多种细胞效应，将凝血系统与炎症反应联系起来。发现首个功能性凝血酶受体需要多年研究，该受体具有独特的激活机制。该受体被命名为蛋白酶激活受体1（PAR-1），因为其激活需要蛋白水解作用。随后的研究导致了其他PARs的鉴定，即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也可被凝血酶激活。蛋白酶对PARs的激活涉及蛋白水解切割以及氨基末端受体序列的暴露，该序列通过与受体的第二个细胞外环结合作为拴系配体来启动跨膜信号传导。序列分析表明，所有PARs都是7跨膜结构域受体超家族的成员。在大多数组织和众多细胞中都检测到了PARs的表达，因此这些分子与多种生理过程以及多种疾病的发病机制有关。
