Induction of c‐fos gene expression by urokinase‐type plasminogen activator in human ovarian cancer cells

Abstract

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.