Differential activation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors

EMBO J. 1995 Oct 16;14(20):5037-47. doi: 10.1002/j.1460-2075.1995.tb00186.x.


The upstream regulatory region of the c-fos promoter contains two growth factor-regulated promoter elements: the serum response element, which binds a ternary complex comprising serum response factor (SRF) and a ternary complex factor (TCF); and the sis-inducible element (SIE) which binds STAT transcription factors. We used transient transfection of c-fos promoter mutants in NIH 3T3 cells to assess the contributions of these elements to activation by different extracellular stimuli. Colony-stimulating factor-1, platelet-derived growth factor and epidermal growth factor activate the c-fos promoter via cooperation of the SIE and the SRE; however, mutants that can bind SRF but not STATs or TCF remain inducible by whole serum. Activation by the SIE is context-dependent: interferons activate STAT DNA binding activity and transcription of SIE reporter genes, but not the c-fos promoter, which requires an additional ras-dependent signal. SRE activation by receptor tyrosine kinases requires TCF binding, and can be mediated by the TCF Elk-1. In contrast, SRE activation following activation of heterotrimeric G proteins by lysophosphatidic acid or aluminium fluoride ion requires SRF but is independent of TCF binding. These results suggest that heterotrimeric G proteins activate a signalling pathway distinct from those that activate the STATs and the TCFs, that controls SRF activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • DNA-Binding Proteins / metabolism
  • Epidermal Growth Factor / pharmacology
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Humans
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Platelet-Derived Growth Factor / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-sis
  • Recombinant Proteins / biosynthesis
  • Serum Response Factor
  • Signal Transduction*
  • Transcription Factors / metabolism
  • Transfection


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-sis
  • Recombinant Proteins
  • Serum Response Factor
  • Transcription Factors
  • Epidermal Growth Factor
  • Macrophage Colony-Stimulating Factor
  • GTP-Binding Proteins