Regulation of Ki-ras expression in Reuber H35 cells.
Glucagon at a low concentration has a stimulatory effect on Ki-ras expression, whereas, at high concentrations the hormone suppresses the level of the Ki-ras transcripts. Incubation of the hepatoma cells with 10 microM dibutyryl cyclic AMP results in suppression of Ki-ras expression but the phorbol ester, 21-O-tetradecanoylphorbol 13-acetate (TPA) causes an increase. Down regulation of protein kinase C by prolonged exposure of hepatoma cells to TPA causes a dramatic decrease in the glucagon-stimulated effect on Ki-ras expression. The presence of diacylglycerol for 2 h in the culture medium results in a significant increase in Ki-ras expression, while treatment of the cells with 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine, a potent inhibitor of protein kinase C, leads to a dramatic reduction. The calcium ionophore, A23187 is able to stimulate Ki-ras expression, whereas, addition of verapamil or EGTA results in its suppression. The present findings suggest that the inductive effect of glucagon on Ki-ras expression at low concentrations is via the activation of protein kinase C which causes phosphorylation of some regulatory proteins that may eventually affect the level of Ki-ras mRNA. The suppressive effect of glucagon at higher concentrations is via an increase in cAMP through activation of adenylate cyclase.
Chan
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SO
Department of Biochemistry, University of Hong Kong.
Wong
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SS
Yeung
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DC
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D015342:DNA Probes; D004075:Diglycerides / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D015342:DNA Probes; D004075:Diglycerides; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012334:RNA, Neoplasm; D000001:Calcimycin; D004533:Egtazic Acid; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D005934:Glucagon; D014700:Verapamil; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium