ras p21 oncoprotein is autoregulated and acts as a potential mediator of insulin action or the H-ras1 promoter.
Rat fibroblast cells carrying an exogenous normal or mutant T24 human H-ras1 gene were transfected with plasmids carrying the normal or mutant T24 H-ras1 gene promoter linked to the reporter chloramphenicol acetyl transferase (CAT) gene and the cells were treated with insulin. We found that the H-ras1 gene was positively autoregulated and that insulin potentiated the response of the T24 ras p21 to the H-ras1 gene promoter. We have also examined the effect of insulin directly on the H-ras1 promoter by treating stable transfectants obtained after transfection of rat fibroblasts with plasmids carrying the normal or mutant T24 H-ras1 gene promoter linked to the reporter CAT gene and the selectable marker aminoglycoside phosphotransferase (aph) gene. We found that insulin appeared to have no direct effect on the H-ras1 promoter in this case, suggesting that the effect is mediated through the ras p21 oncogene product. We suggest that the mutant T24 H-ras p21 protein mediates the action of insulin.
Pintzas
A
A
Hellenic Pasteur Institute, Athens, Greece.
Spandidos
D A
DA
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase; D005786:Gene Expression Regulation; D011905:Genes, ras / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D011995:Recombination, Genetic; D014162:Transfection
D007328:Insulin; D011518:Proto-Oncogene Proteins; D015500:Chloramphenicol O-Acetyltransferase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)