Open AccessRegulation of Ki‐ ras expression in Reuber H35 cells
Author(s) -
CHAN SaiOn,
WONG Susanna SiuChun,
YEUNG Desmond ChakYew
Publication year - 1990
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1990.tb19387.x
Subject(s) - glucagon , egta , diacylglycerol kinase , protein kinase c , adenylate kinase , protein kinase a , endocrinology , medicine , cyclase , chemistry , second messenger system , kinase , biology , signal transduction , calcium , hormone , biochemistry , stimulation , receptor
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 μM 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.