A UROKINASE-SENSITIVE REGION OF THE HUMAN UROKINASE RECEPTOR IS RESPONSIBLE FOR ITS CHEMOTACTIC ACTIVITY

The role of urokinase-type plasminogen activator (uPA) and its recepto r (uPAR/CD87) in cell migration and invasion is well substantiated, Re cently, uPA has been shown to be essential in cell migration, since uP A(-/-) mice are greatly impaired in inflammatory cell recruitment, We have shown previously that the uPA-induced chemotaxis requires interac tion with and modification of uPAR/CD87, which is the true chemoattrac ting molecule acting through an unidentified cell surface component wh ich mediates this cell surface chemokine activity, By expressing and t esting several uPAR/CD87 variants, we have located and functionally ch aracterized a potent uPAR/CD87 epitope that mimics the effects of the uPA-uPAR interaction, The chemotactic activity lies in the region link ing domains 1 and 2, the only protease-sensitive region of uPAR/CD87, efficiently cleaved by uPA at physiological concentrations. Synthetic peptides carrying this epitope promote chemotaxis and activate p56/p59 (hck) tyrosine kinase. Both chemotaxis and kinase activation are pertu ssis toxin sensitive, involving a G(i/o) protein in the pathway.