UROKINASE--A LINK BETWEEN CELL ADHESION AND PROTEOLYSIS

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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.