Induction of urokinase-type plasminogen activator by fibroblast growth factor (FGF)-2 is dependent on expression of FGF receptors and does not require activation of phospholipase Cgamma1.
The roles of heparan sulfate proteoglycans and tyrosine kinase fibroblast growth factor (FGF) receptors in mediating the induction of plasminogen activator (PA) by FGF-2 were investigated using L6 myoblast cells that normally do not express detectable FGF receptors. PA was induced by FGF-2 in a dose-dependent manner in L6 cells expressing transfected FGF receptor-1 but not in nontransfected cells or cells transfected with the vector alone. The PA produced in these cells was characterized as urokinase-type PA (uPA). Thus, expression of a tyrosine kinase FGF receptor was required for induction of uPA. Internalization of FGF through heparan sulfates does not seem to be involved in this response as soluble heparin and suramin at concentrations which inhibited FGF-2 binding to heparan sulfates but not receptors did not affect the induction of uPA by FGF-2. Mutant receptors in which the tyrosine kinase was inactivated were not able to respond to FGF-2. In contrast, mutation of the site of phospholipase Cgamma1 (PLCgamma) binding in the receptor, which causes loss of PLCgamma activation, had no effect on uPA induction by FGF-2. These results suggest that PLCgamma activation is not required for induction of uPA by FGF-2.
Roghani
M
M
Department of Cell Biology, New York University Medical Center, New York, New York 10016, USA.
Mohammadi
M
M
Schlessinger
J
J
Moscatelli
D
D
D002704:Chlorates / Q000494:pharmacology; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D051966:Phospholipase C gamma; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D002704:Chlorates; D007527:Isoenzymes; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D013498:Suramin; D006493:Heparin; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D014568:Urokinase-Type Plasminogen Activator