Kjøller Lars
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Biol Chem. 2002 Jan;383(1):5-19. doi: 10.1515/BC.2002.002.
Cell migration is a complex process requiring tight control of several mechanisms including dynamic reorganization of the actin cytoskeleton and adhesion to the extracellular matrix. The GPI-anchored urokinase plasminogen activator receptor (uPAR) has an important role in the regulation of cell motility in many cell types. This is partly due to the localization of proteolytic activity on the cell surface by binding of the serine protease uPA. Results accumulated over the last decade suggest that uPAR is also involved in motility control through other mechanisms. These include induction of signal transduction events after ligation with uPA, binding to the extracellular matrix molecule vitronectin (VN), and association with integrins and other transmembrane partners. In this review these mechanisms will be discussed with a special emphasis on how the GPI-linked receptor transmits signals to the intracellular milieu and how uPAR participates in the regulation of actin cytoskeleton reorganization and cell adhesion during cell migration.
细胞迁移是一个复杂的过程,需要对多种机制进行严格控制,包括肌动蛋白细胞骨架的动态重组以及与细胞外基质的黏附。糖基磷脂酰肌醇(GPI)锚定的尿激酶型纤溶酶原激活物受体(uPAR)在多种细胞类型的细胞运动调节中发挥着重要作用。这部分是由于丝氨酸蛋白酶uPA的结合使蛋白水解活性定位于细胞表面。过去十年积累的研究结果表明,uPAR还通过其他机制参与运动控制。这些机制包括与uPA结合后诱导信号转导事件、与细胞外基质分子玻连蛋白(VN)结合以及与整合素和其他跨膜伴侣相互作用。在这篇综述中,将讨论这些机制,特别强调GPI连接的受体如何将信号传递到细胞内环境,以及uPAR如何在细胞迁移过程中参与肌动蛋白细胞骨架重组和细胞黏附的调节。