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.

该研究提案是一个多方面的项目和细胞迁移。 细胞相关蛋白水解中的中心元件对细胞的重要性 迁移和组织重塑是尿激酶（uPA）及其细胞表面 受体的 我们以前已经证明， 单核细胞依赖于uPA受体占有率， uPA抑制剂纤溶酶原激活物抑制剂1（派-1） 通过uPA/派复合物周转。 我们最近描述了一部小说 玻连蛋白受体，其活性与uPA受体占有率偶联。 由于玻连蛋白的已知功能是结合派-1，我们假设， uPA诱导的玻连蛋白结合启动细胞附着， 增强uPA/派-1复合物的形成调节uPA依赖性 蛋白水解并引发随后的细胞脱离。 为了验证这一 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在细胞周围的重要性 蛋白水解和细胞迁移。