Induction of c-fos gene expression by urokinase-type plasminogen activator in human ovarian cancer cells.
Binding of urokinase-type plasminogen activator (u-PA) to u-PA receptor (u-PAR) induces the rapid and transient expression of c-fos in OC-7 ovarian carcinoma cells. The pretreatment of the cells with protein tyrosine kinase (PTK) inhibitors, but not the inactivation of the u-PA active site by DFP (diisopropyl fluorophosphate), abrogates this effect. A soluble u-PAR fragment, expressed in baculovirus-infected Sf9 cells and purified by affinity chromatography, competes for binding of u-PA to u-PAR and inhibits c-fos induction. We conclude that activation of u-PAR after interaction with u-PA at the cell surface initiates a transmembrane signal, most likely in conjunction with other still unknown protein(s). This signal generates PTK activity feeding into a signal transduction pathway which activates nuclear transcription factors.
Dumler
I
I
Institute of Cellular and Molecular Biology, Schering AG, Berlin, Germany.
Petri
T
T
Schleuning
W D
WD
D001665:Binding Sites; D001667:Binding, Competitive; D015152:Blotting, Northern; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D010960:Plasminogen Activators / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
C524898:PLAUR protein, human; D016760:Proto-Oncogene Proteins c-fos; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator