UROKINASE PLASMINOGEN-ACTIVATOR INDUCES SMOOTH-MUSCLE CELL-MIGRATION - KEY ROLE OF GROWTH FACTOR-LIKE DOMAIN

We defined the role of urokinase plasminogen activator (uPA) and its g rowth factor-like domain (GFD) in stimulating smooth muscle cell (SMC) migration. Recombinant uPA (r-uPA) stimulated migration approximately 3-fold whilst the recombinant uPA mutant containing an altered GFD (r -uPAmut) was ineffective. Both uPA variants bound to the same high aff inity receptor in a competitive manner. FGF-2- and PDGF-BB-induced mig ration was also dependent on uPA, their effects being antagonized by a ddition of a uPA-neutralizing antibody or the r-uPAmut. Thus r-uPA is chemotactic for SMC and stimulation of cell migration by PDGF-BB and F GF-2 is dependent on uPA. The GFD of uPA is essential for its chemotac tic effects. (C) 1997 Federation of European Biochemical Societies.