Fibroblast growth factor-dependent mitogenic signal transduction pathway in chemically transformed mouse fibroblasts is similar to but distinct from that initiated by phorbol esters.
Treatment of the quiescent, chemically transformed Balb/c mouse 3T3 cells (BP-A31) with fibroblast growth factor (FGF) leads to reinitiation of the cell division cycle in a large proportion of the cells. The characteristics of the mitogenic action of FGF closely resemble those of phorbol esters (activators of protein kinases type C) and differ from those of insulin (mediated by insulin-like growth factor 1 receptors). In particular, the effects of FGF as well as of phorbol-2-myristate-13-acetate (PMA), unlike the effects of insulin, are prevented by a low concentration (7.5 nM) of staurosporin (an efficient inhibitor of protein kinase C) as well as by 3-isobutyl-1-methyl xanthin (IBMX). Both FGF and PMA are good inducers of the accumulation of c-fos and c-jun mRNAs, whereas insulin has little effect. However, FGF was fully active (both as a mitogen and as inducer of c-fos mRNA accumulation) also in cells where the protein kinase C-mediated pathway had been downregulated by a long exposure to phorbol dibutyrate. We propose that the mitogenic effect of FGF does not require activation of protein kinase C, but that the subsequent events in the transduction pathways initiated by FGF and PMA, respectively, are (in part) coincident.
INSERM U 55, Hôpital St.-Antoine, Paris, France.
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Buchou
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Mĕster
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D015398:Signal Transduction; D019311:Staurosporine; D014157:Transcription Factors / Q000235:genetics; D014404:Tubulin / Q000235:genetics
D000470:Alkaloids; D004268:DNA-Binding Proteins; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D014404:Tubulin; D005346:Fibroblast Growth Factors; D003513:Cycloheximide; D011493:Protein Kinase C; D019311:Staurosporine; D015056:1-Methyl-3-isobutylxanthine