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Urokinase plasminogen activator induces smooth muscle cell migration: key role of growth factor-like domain
V Stepanova1, A Bobik, R Bibilashvily
1Laboratory of Molecular Endocrinology, Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
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.