UROKINASE--A LINK BETWEEN CELL ADHESION AND PROTEOLYSIS

该研究提案是一个多方面的项目和细胞迁移。 细胞相关蛋白分解中对细胞重要的中心成分 尿激酶型纤溶酶原激活剂及其细胞表面迁移与组织重塑 受体。我们之前已经证明了它的粘附性 单核细胞依赖于uPA受体的占位并被调节 纤溶酶原激活物抑制物-1(PAI-1) 通过uPA/PAI复合体周转。我们最近描述了一部小说 Vitronectin受体的活性与uPA受体的占有率有关。 由于Vitronectin的一个已知功能是结合PAI-1，我们假设 UPA诱导的Vitronectin结合启动细胞附着，并通过 增强uPA/PAI-1复合体的形成调节uPA依赖 蛋白质分解并启动随后的细胞分离。为了测试这一点 假设我们将确定Vitronectin受体的特征并确定 尿激酶型纤溶酶原激活剂诱导的玻璃连结蛋白与细胞周膜结合的重要性 蛋白质分解和细胞迁移。

The research proposal is a multifaceted project and cellular migration. Central elements in cell-associated proteolysis important to cell migration and tissue remodeling are urokinase (uPA) and its cell-surface receptor. We have previously demonstrated that the adhesiveness of monocytic cells is dependent upon uPA receptor occupancy and regulated by the uPA inhibitor plasminogen activator inhibitor type 1 (PAI-1) through uPA/PAI complex turnover. We have recently described a novel vitronectin receptor whose activity is coupled to uPA receptor occupancy. As a known function of vitronectin is to bind PAI-1, we hypothesize that uPA-induced vitronectin binding initiates cellular attachment and by potentiating uPA/PAI-1 complex formation regulates uPA-dependent proteolysis and initiates subsequent cell detachment. To test this hypothesis we will characterize the vitronectin receptor and determine the importance of uPA-induced vitronectin binding on pericellular proteolysis and cellular migration.