Department of Pathology, University of California, San Diego, California.
Am J Physiol Cell Physiol. 2021 Oct 1;321(4):C721-C734. doi: 10.1152/ajpcell.00269.2021. Epub 2021 Aug 18.
Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are serine proteases and major activators of fibrinolysis in mammalian systems. Because fibrinolysis is an essential component of the response to tissue injury, diverse cells, including cells that participate in the response to injury, have evolved receptor systems to detect tPA and uPA and initiate appropriate cell-signaling responses. Formation of functional receptor systems for the plasminogen activators requires assembly of diverse plasma membrane proteins, including but not limited to: the urokinase receptor (uPAR); integrins; -formyl peptide receptor-2 (FPR2), receptor tyrosine kinases (RTKs), the -methyl-d-aspartate receptor (NMDA-R), and low-density lipoprotein receptor-related protein-1 (LRP1). The cell-signaling responses elicited by tPA and uPA impact diverse aspects of cell physiology. This review describes rapidly evolving knowledge regarding the structure and function of plasminogen activator receptor assemblies. How these receptor assemblies regulate innate immunity and inflammation is then considered.
组织型纤溶酶原激活物（tPA）和尿激酶型纤溶酶原激活物（uPA）是丝氨酸蛋白酶，是哺乳动物系统中纤维蛋白溶解的主要激活剂。由于纤维蛋白溶解是组织损伤反应的一个重要组成部分，包括参与损伤反应的细胞在内的各种细胞都进化出了受体系统来检测 tPA 和 uPA，并启动适当的细胞信号反应。纤溶酶原激活物功能性受体系统的形成需要组装多种质膜蛋白，包括但不限于：尿激酶受体（uPAR）；整合素；甲酰肽受体-2（FPR2），受体酪氨酸激酶（RTKs），-甲基-d-天冬氨酸受体（NMDA-R）和低密度脂蛋白受体相关蛋白-1（LRP1）。tPA 和 uPA 引发的细胞信号反应影响细胞生理学的各个方面。本综述描述了关于纤溶酶原激活物受体组装的结构和功能的快速发展的知识。然后考虑了这些受体组装如何调节先天免疫和炎症。
