UROKINASE--A LINK BETWEEN CELL ADHESION AND PROTEOLYSIS

尿激酶——细胞粘附和蛋白质水解之间的联系

• 批准号: 2445010
• 负责人: DAVID A WALTZ
• 金额: $ 8.37万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2445010
• 关键词: cell adhesion; cell migration; crosslink; drug receptors; enzyme linked immunosorbent assay; monocyte; plasminogen activator; plasminogen activator inhibitors; polymerase chain reaction; protein sequence; proteolysis; receptor binding; receptor expression; tissue /cell culture; urokinase; vitronectin; western blottings

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.

该研究计划是一个多方面的项目和细胞迁移。 对细胞很重要的细胞相关蛋白水解的核心元件 迁移和组织重塑是尿激酶（uPA）及其细胞表面 受体。 我们之前已经证明了 单核细胞依赖于 uPA 受体占据并受到调节 由 uPA 抑制剂纤溶酶原激活剂抑制剂 1 型 (PAI-1) 通过 uPA/PAI 复合体周转。 我们最近描述了一部小说 玻连蛋白受体，其活性与 uPA 受体占据相关。 由于玻连蛋白的已知功能是结合 PAI-1，我们假设 uPA 诱导的玻连蛋白结合启动细胞附着并通过 增强 uPA/PAI-1 复合物形成调节 uPA 依赖性 蛋白水解并启动随后的细胞分离。 为了测试这个 假设我们将表征玻连蛋白受体并确定 uPA 诱导的玻连蛋白结合细胞周的重要性 蛋白水解和细胞迁移。