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

FEBS Letters

Petri, T.¹  Schleuning, W.-D.¹  Dumler, I.¹ 

[1] Institute of Cellular and Molecular Biology, Schering AG, Müllerstr. 170, 13342 Berlin, Germany

关键词: Immediate early gene expression;    Plasminogen activator;    Urokinase-type plasminogen activator receptor;    Human ovarian cancer cell;    Signal transduction;    u-PA;    urokinase-type plasminogen activator;    u-PAR;    u-PA receptor;    PTK;    protein tyrosine kinase;    PMA;    phorbol 12-myristate acetate;    DFP;    diisopropyl fluorophosphate;    PBS;    phosphate-buffered saline;    SDS;    sodium dodecylsulphate;    PAGE;    polyacrylamide gel electrophoresis;    DTT;    dithiothreitol;    BSA;    bovine serum albumin;    FSC;    fetal calf serum;    SSC;    0.15 M NaCl/0.015 M Na3-citrate;    pH 7.O;   

DOI  :  10.1016/0014-5793(94)80298-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown