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 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.
Stepanova
V
V
Laboratory of Molecular Endocrinology, Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Bobik
A
A
Bibilashvily
R
R
Belogurov
A
A
Rybalkin
I
I
Domogatsky
S
S
Little
P J
PJ
Goncharova
E
E
Tkachuk
V
V
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D000077214:Becaplermin; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D003001:Cloning, Molecular; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000737:chemistry*; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000494:pharmacology; D017540:Tunica Media / Q000187:drug effects / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D006133:Growth Substances; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; C524900:Plaur protein, rat; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D014568:Urokinase-Type Plasminogen Activator