Maly K, Uberall F, Loferer H, Doppler W, Oberhuber H, Groner B, Grunicke H H
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
J Biol Chem. 1989 Jul 15;264(20):11839-42.
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.
在静止的转染了Ha-ras基因的NIH 3T3细胞中，添加血清生长因子、蛙皮素或12-O-十四酰佛波醇-13-乙酸酯（TPA）会导致一种对二甲苯磺酰胺敏感的细胞内碱化，这种碱化可被蛋白激酶C的强效抑制剂星形孢菌素抑制。转化型Ha-ras基因的表达会导致细胞质pH值在不依赖生长因子的情况下升高。这种由Ha-ras诱导的碱化对二甲苯磺酰胺敏感，但不受星形孢菌素浓度的影响，而星形孢菌素浓度可在添加生长因子或TPA后阻止pH反应。长期暴露于TPA导致蛋白激酶C耗竭，消除了对蛙皮素和佛波酯的pH反应，但不影响Ha-ras诱导的细胞内碱化。结论是，Ha-ras的表达通过一种尚未明确的不依赖蛋白激酶C的机制导致Na+/H+反向转运体的激活。
