title: Transforming growth factor-beta1 and protein kinase C synergistically activate the c-fos serum response element in myocardial cells.
abstract: We previously reported that transforming growth factor-beta1 (TGF-beta1) potentiated alpha1-adrenergic and stretch-induced c-fos mRNA expression and norepinephrine (NE)-induced amino acid incorporation in rat cultured myocardial cells (MCs). In the present study, we attempted to explore the mode of TGF-beta1 action for c-fos gene expression in MCs. In the transient transfection assay, TGF-beta1 potentiated NE- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated c-fos promoter/enhancer, but not forskolin-activated c-fos promoter/enhancer. The c-fos serum response element (SRE) and the TPA response element (TRE) were responsible for TGF-beta1-induced potentiation of the NE or TPA action. Although TGF-beta1 activated not only the wild-type c-fos SRE, but also the mutated c-fos SRE, which contains an intact binding site for the serum response factor (SRF) but lacks the ternary complex factor (TCF) binding site, TPA activated the wild-type c-fos SRE but not the mutated c-fos SRE. TGF-beta1 did not potentiate the effects of TPA on the activation of mitogen-activated protein kinase (MAPK) and the phosphorylation of Elk-1 and SAP-1a, which belong to TCF at the c-fos SRE. These results indicate that TGF-betaf potentiates the c-fos SRE activated by PKC through the SRF binding site. TGF-beta1 is involved in the regulation of c-fos gene expression through the c-fos SRE and is subsequently involved in the regulation of the gene which has the TRE in the promoter/enhancer region.
authors.affiliation: The First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ueyama
authors.forename: S
authors.initials: S
authors.lastname: Kawashima
authors.forename: T
authors.initials: T
authors.lastname: Sakoda
authors.forename: K I
authors.initials: KI
authors.lastname: Hirata
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.forename: W
authors.initials: W
authors.lastname: Yamochi
authors.forename: H
authors.initials: H
authors.lastname: Akita
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D026362:Serum Response Factor; D014157:Transcription Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4
chemical_list: D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009638:Norepinephrine