Activation of the serum response element and 12-O-tetradecanoylphorbol-13-acetate response element by the activated c-raf-1 protein in a manner independent of protein kinase C.
Transfection of the cDNA encoding the activated c-raf-1 protein or addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) or dibutyryl cAMP to NIH/3T3 cells activated the c-fos gene enhancer linked to the chloramphenicol acetyltransferase or luciferase reporter gene. Prolonged treatment of NIH/3T3 cells with phorbol 12,13-dibutyrate caused down-regulation of protein kinase C. In these cells, addition of TPA did not stimulate the c-fos gene enhancer any more, but transfection of the c-raf-1 cDNA or addition of dibutyryl cAMP still stimulated the c-fos gene enhancer to the same extent as those induced in the control cells. Transfection of the c-raf-1 cDNA or addition of TPA to NIH/3T3 cells stimulated the serum response element and TPA response element but not the cAMP response element. In contrast, addition of dibutyryl cAMP to NIH/3T3 cells stimulated the cAMP response element but not the serum response element or TPA response element. These results indicate that the activated c-raf-1 protein stimulates the serum response element and TPA response element in a manner independent of protein kinase C and cAMP-dependent protein kinase. Since the c-fos gene enhancer has been shown to contain the serum response element and cAMP response element, it is most likely that the c-raf-1 protein is involved in the regulation of c-fos gene expression through the serum response element.
Kaibuchi
K
K
Department of Biochemistry, Kobe University School of Medicine, Japan.
Fukumoto
Y
Y
Oku
N
N
Hori
Y
Y
Yamamoto
T
T
Toyoshima
K
K
Takai
Y
Y
D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D019908:Proto-Oncogene Proteins c-raf; D011519:Proto-Oncogenes; D026362:Serum Response Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection
D003470:Culture Media; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D003994:Bucladesine; D011505:Protein-Tyrosine Kinases; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate