Urokinase plasminogen activator induces smooth muscle cell migration: key role of growth factor‐like domain

Abstract

We defined the role of urokinase plasminogen activator (uPA) and its growth 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 affinity receptor in a competitive manner. FGF-2- and PDGF-BB-induced migration was also dependent on uPA, their effects being antagonized by addition 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 FGF-2 is dependent on uPA. The GFD of uPA is essential for its chemotactic effects.