Ha-ras activates the Na+/H+ antiporter by a protein kinase C-independent mechanism.
In quiescent Ha-ras-transfected NIH 3T3 cells, addition of serum growth factors, bombesin or 12-O-tetradecanoylphorbol-13-acetate (TPA) leads to a dimethylamiloride-sensitive intracellular alkalinization which can be inhibited by staurosporine, a potent inhibitor of protein kinase C. Expression of the transforming Ha-ras gene causes a growth factor-independent increase in cytoplasmic pH. This Ha-ras-induced alkalinization is sensitive to dimethylamiloride but is not affected by staurosporine concentrations which prevent the pH response after addition of growth factors or TPA. Protein kinase C depletion by long term exposure to TPA eliminates the pH response to bombesin and phorbol ester but does not effect the Ha-ras-induced intracellular alkalinization. It is concluded that expression of Ha-ras causes an activation of the Na+/H+ antiporter by an as yet unknown protein kinase C-independent mechanism.
Maly
K
K
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Uberall
F
F
Loferer
H
H
Doppler
W
W
Oberhuber
H
H
Groner
B
B
Grunicke
H H
HH
D000470:Alkaloids / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts; D011905:Genes, ras; D006133:Growth Substances / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D000470:Alkaloids; D002352:Carrier Proteins; D006133:Growth Substances; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin