Selected Publication:
Maly, K; Hochleitner, B; Uberall, F; Loferer, H; Oberhuber, H; Doppler, W; Grunicke, H.
Mechanism and biological significance of the Ha-ras-induced activation of the Na+/H(+)-antiporter.
Adv Enzyme Regul. 1990; 30(3):63-74
Doi: 10.1016/0065-2571(90)90009-Q
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- Co-authors Med Uni Graz
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Hager Boris
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- Abstract:
- Expression of the transforming Ha-ras oncogene in MMTV-LTR transfected NIH 3T3 cells leads to a growth factor independent activation of the Na+/H(+)-antiporter. The activation of the antiporter is insensitive to the protein kinase inhibitor staurosporine and equally expressed in protein kinase C-depleted cells. It is concluded that the Ha-ras induced activation of the antiporter occurs by a protein kinase C-independent mechanism. An inhibition of the Na+/H(+)-antiporter by dimethylamiloride or a reduction of the extracellular [Na+] concentration results in a depression of the bombesin induced release of Ca2+ from intracellular stores. These results are explained by a steep pH-dependence of the Ca2(+)-mobilizing system which exhibits a maximum at pH 7.1 in the system studied here. Stimulation by growth factors of quiescent cells with a resting pH below 7 results in a shift of the cytosolic pH towards the optimum for the Ca2+ release. In agreement with the proposed interrelationship, pHi and [Ca2+]i rise and peak simultaneously after addition of bombesin to G0 arrested cells.
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