Desensitization of the Ca2+-mobilizing system to serum growth factors by Ha-ras and v-mos.
An elevation of the intracellular pH and a rise in the cytoplasmic Ca2+ concentration are considered important mitogenic signals which are observed after stimulation by various growth factors. In a preceding report it was demonstrated that the expression of Ha-ras or v-mos in cells transfected with Ha-ras or v-mos, respectively, leads to an activation of the Na+/H+ antiporter and a concomitant rise in intracellular pH (W. Doppler, R. Jaggi, and B. Groner, Gene 54:145-151, 1987). This report describes the effect of the Ha-ras and v-mos oncogenes on intracellular Ca2+ release. The expression of Ha-ras in NIH 3T3 cells carrying a glucocorticoid-inducible transforming Ha-ras gene caused a desensitization of the Ca2+-mobilizing system to serum growth factors. The induction of p21ras in cells carrying the corresponding glucocorticoid-inducible proto-oncogene did not affect the Ca2+ response to growth factors. Conditions leading to the expression of the transforming Ha-ras gene but not those causing the induction of the normal Ha-ras gene yielded an increase in phosphatidylinositol turnover and a concomitant rise in inositol phosphates. Results similar to those obtained with the transforming Ha-ras gene were seen after the expression of v-mos. The data are consistent with a mechanism in which expression of the transforming Ha-ras gene leads to a release of Ca2+ from intracellular stores via elevated levels of inositol trisphosphate.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras; D006133:Growth Substances / Q000097:blood / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism*; D051379:Mice; D009857:Oncogenes; D010716:Phosphatidylinositols / Q000378:metabolism; D013403:Sugar Phosphates / Q000378:metabolism*
D006133:Growth Substances; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D013403:Sugar Phosphates; D003907:Dexamethasone; D019204:GTP-Binding Proteins; D002118:Calcium