Activation of the c-fos promoter by increased internal pH

J Cell Biochem. 1995 Apr;57(4):630-40. doi: 10.1002/jcb.240570407.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adenosine Triphosphatases / biosynthesis
  • Adenosine Triphosphatases / genetics
  • Animals
  • Base Sequence
  • Cattle
  • Colforsin / pharmacology
  • Culture Media
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Electrophoresis
  • Endopeptidases*
  • Genes, fos*
  • Hydrogen-Ion Concentration
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Oncogene Proteins*
  • Oncogene Proteins, Fusion / biosynthesis
  • Oncogene Proteins, Fusion / genetics
  • Promoter Regions, Genetic*
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Proton Pumps / drug effects*
  • Serum Response Factor
  • Tissue Plasminogen Activator / pharmacology
  • Transcription Factor AP-1 / biosynthesis
  • Transcription Factor AP-1 / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcriptional Activation / drug effects*
  • Transfection
  • Ubiquitin Thiolesterase

Substances

  • Culture Media
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Oncogene Proteins
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Proton Pumps
  • Serum Response Factor
  • Transcription Factor AP-1
  • Transcription Factors
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Endopeptidases
  • USP6 protein, human
  • Ubiquitin Thiolesterase
  • Tissue Plasminogen Activator
  • Adenosine Triphosphatases