Chapman H A, Wei Y
Pulmonary and Critical Care Division, University of California at San Francisco, 94143-0130, USA.
Thromb Haemost. 2001 Jul;86(1):124-9.
Migratory cells use both adhesion receptors and proteolytic enzymes to regulate their interaction with and response to extracellular matrices. Cooperation between integrins and proteases operates at several levels: integrin signaling induces proteases, proteases co-localize with integrins, and proteases regulate the interface between integrins and the intracellular cytoskeleton. One protease system intimately connected to integrins is the urokinase/urokinase receptor(uPAR)/plasmin system. Recent studies indicate urokinase promotes the ligand-like binding of its receptor to a set of beta1 and beta2 integrins, this binding in turn affecting integrin signaling and cell migration. The glycolipid anchor of uPAR associates with cholesterol-rich membrane rafts. Binding of uPAR to integrins may enrich integrin clusters with signaling molecules such as src-family kinases that localize to rafts and are important to integrin function. Signals derived from integrin/uPAR complexes promote the function of other integrins. Thus the urokinase/plasmin system coordinates with integrins to regulate cell: matrix interactions.
迁移细胞利用黏附受体和蛋白水解酶来调节它们与细胞外基质的相互作用及反应。整合素与蛋白酶之间的协同作用在多个层面发挥作用：整合素信号传导诱导蛋白酶产生，蛋白酶与整合素共定位，并且蛋白酶调节整合素与细胞内细胞骨架之间的界面。与整合素密切相关的一个蛋白酶系统是尿激酶/尿激酶受体（uPAR）/纤溶酶系统。最近的研究表明，尿激酶促进其受体与一组β1和β2整合素的类配体结合，这种结合进而影响整合素信号传导和细胞迁移。uPAR的糖脂锚与富含胆固醇的膜筏相关联。uPAR与整合素的结合可能会使整合素簇富集信号分子，如定位于膜筏且对整合素功能很重要的src家族激酶。源自整合素/uPAR复合物的信号促进其他整合素的功能。因此，尿激酶/纤溶酶系统与整合素协同作用以调节细胞与基质的相互作用。
