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.
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.
Sakoda
T
T
Department of Biochemistry, Kobe University School of Medicine, Japan.
Kaibuchi
K
K
Kishi
K
K
Kishida
S
S
Doi
K
K
Hoshino
M
M
Hattori
S
S
Takai
Y
Y
D016475:3T3 Cells; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D004742:Enhancer Elements, Genetic; D019204:GTP-Binding Proteins / Q000032:analysis / Q000502:physiology*; D016762:Genes, fos; D006160:Guanosine Triphosphate / Q000378:metabolism; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D015398:Signal Transduction; D020668:rap GTP-Binding Proteins
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D008156:Luciferases; D019908:Proto-Oncogene Proteins c-raf; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras); D020668:rap GTP-Binding Proteins