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 recepto r (u-PAR) induces the rapid and transient expression of c-Sos in OC-7 ovarian carcinoma cells. The pretreatment of the cells with protein ty rosine kinase (PTK) inhibitors, but not the inactivation of the u-PA a ctive site by DFP (diisopropyl fluorophosphate), abrogates this effect . A soluble u-PAR fragment, expressed in baculovirus-infected Sf9 cell s and purified by affinity chromatography, competes for binding of u-P A to u-PAR and inhibits c-fos induction. We conclude that activation o f u-PAR after interaction with u-PA at the cell surface initiates a tr ansmembrane signal, most likely in conjunction with other still unknow n protein(s). This signal generates PTK activity feeding into a signal transduction pathway which activates nuclear transcription factors.