smg/rap1/Krev-1 p21s inhibit the signal pathway to the c-fos promoter/enhancer from c-Ki-ras p21 but not from c-raf-1 kinase in NIH3T3 cells

Oncogene. 1992 Sep;7(9):1705-11.


smg/rap1A/Krev-1 p21 cDNA is known to inhibit v-Ki-ras p21-induced cell transformation in NIH3T3 cells, but the inhibitory mechanism is not clear at present. In the present study, we examined the effect of smg p21s on the c-fos promoter/enhancer linked to the luciferase reporter gene (c-fos-luciferase). After transfection of c-fos-luciferase into NIH3T3 cells constitutively expressing c-Ki-ras(val-12) p21 or activated c-raf-1 kinase, expression of c-fos-luciferase was much higher than after transfection into control NIH3T3 cells. Addition of platelet-derived growth factor (PDGF), 12-O-tetradecanoyl phorbol 13-acetate (TPA) or dibutyryl cyclic AMP (Bt2cAMP) to the control NIH3T3 cells stimulated c-fos-luciferase expression. Transfection of the smg p21 cDNAs inhibited the activated ras p21-, PDGF- or TPA-stimulated c-fos-luciferase expression, but did not inhibit the activated c-raf-1 kinase- or Bt2cAMP-stimulated reaction. These results indicate that smg p21s inhibit the signal pathways from the PDGF receptor, protein kinase C, and ras p21s to the c-fos promoter/enhancer, but not those from c-raf-1 kinase and cyclic AMP-dependent protein kinase to the c-fos promoter/enhancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cyclic AMP / physiology
  • Enhancer Elements, Genetic*
  • GTP-Binding Proteins / analysis
  • GTP-Binding Proteins / physiology*
  • Genes, fos*
  • Guanosine Triphosphate / metabolism
  • Luciferases / analysis
  • Luciferases / genetics
  • Mice
  • Platelet-Derived Growth Factor / pharmacology
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins p21(ras) / physiology*
  • Signal Transduction*
  • rap GTP-Binding Proteins


  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Guanosine Triphosphate
  • Cyclic AMP
  • Luciferases
  • Proto-Oncogene Proteins c-raf
  • GTP-Binding Proteins
  • Proto-Oncogene Proteins p21(ras)
  • rap GTP-Binding Proteins