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-Sos 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.