Stimulation of K+ transport systems by Ha-ras.
The expression of Ha-ras in quiescent NIH3T3 cells carrying a glucocorticoid-inducible human Ha-ras gene (Val-Gly mutation at codon 12) stimulates total 86Rb+ influx. This effect is predominantly due to an elevated 86Rb+ uptake through an ouabain-resistant, furosemide-sensitive system. The ouabain-sensitive Na+/K(+)-ATPase is less affected. The transport which is resistant to both inhibitors is not altered by Ha-ras. Overexpression of the Ha-ras proto-oncogene causes only a marginal increase in total 86Rb+ uptake. The stimulation of the furosemide-sensitive influx by Ha-ras is paralleled by an increase in mean cell volume which can be inhibited by furosemide. A rapid stimulation of the furosemide-sensitive Rb+ influx is also observed after addition of bombesin to growth-arrested cells. Furosemide inhibits the mitogenic response after expression of Ha-ras or addition of bombesin. Both the Ha-ras and the bombesin-induced stimulation of the furosemide-sensitive Rb+ transport can be blocked by protein kinase C depletion or the protein kinase C inhibitor staurosporine. In contrast to bombesin-induced phosphatidylinositol-4,5-bisphosphate hydrolysis which is down-modulated by Ha-ras, the stimulation of the furosemide-sensitive Rb+ influx by bombesin is elevated in Ha-ras-expressing cells. This is in accordance with the increased mitogenic activity of bombesin in Ha-ras-expressing cells.
Meyer
M
M
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Maly
K
K
Uberall
F
F
Hoflacher
J
J
Grunicke
H
H
D000818:Animals; D001693:Biological Transport, Active; D015153:Blotting, Western; D001839:Bombesin / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D007700:Kinetics; D051379:Mice; D011188:Potassium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D012413:Rubidium / Q000378:metabolism; D014162:Transfection
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D005665:Furosemide; D003907:Dexamethasone; D011493:Protein Kinase C; D012413:Rubidium; D001839:Bombesin; D011188:Potassium