Activation of the c-fos promoter by increased internal pH.
Changes in intracellular pH (pHin) take part in the mitogenic response. Their importance has been stressed by the finding that mouse fibroblasts expressing a yeast proton pumping ATPase (PMA1) exhibit a transformed phenotype and are tumorigenic. These cells do maintain a higher pHin, supporting the idea that elevated pHin may act as a proliferative trigger. Here we show that cells constitutively expressing PMA1 have higher levels of the AP-1 transcription factor. The use of stable transfectants and transient transfection assays show that PMA1 activity induces transactivation of the c-fos promoter. The activation of the promoter is mediated throughout the serum response element (SRE). The use of protein kinase C inhibitors suggests that AP-1 activation is achieved through a pathway independent of protein kinase C.
Murguía
J R
JR
Instituto de Investigaciones Biomédicas del C.S.I.C., Madrid, Spain.
De Vries
L
L
Gomez-García
L
L
Schönthal
A
A
Perona
R
R
D016475:3T3 Cells; D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004586:Electrophoresis; D010450:Endopeptidases; D016762:Genes, fos; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D017494:Proton Pumps / Q000187:drug effects*; D026362:Serum Response Factor; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D043222:Ubiquitin Thiolesterase
D003470:Culture Media; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D017494:Proton Pumps; D026362:Serum Response Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010450:Endopeptidases; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase; D010959:Tissue Plasminogen Activator; D000251:Adenosine Triphosphatases