Effect of Ha-ras on phosphatidylinositol metabolism, Na+/H+-antiporter and mobilization of intracellular calcium.
NIH3T3 cells were transfected with activated Ha-ras and the corresponding proto-oncogene was subjected to transcriptional control by recombination in vitro with MMTV-LTR. Induction of p21ras expression in quiescent cells by dexamethasone causes an increased turnover of phosphatidylinositol 4,5-bisphosphate with a concomitant rise in inositol phosphates, and an activation of the Na+/H+-antiporter. Addition of serum growth factors to dexamethasone treated cells does not result in an additional stimulation of phosphatidylinositol metabolism or Na+/H+-exchange. There is also a desensitization to exogenous growth factors of the intracellular Ca2+-mobilizing system, leading to a depression of the transitory increase in cytosolic Ca2+ after addition of serum growth factors. None of these effects are seen after expression of the Ha-ras proto-oncogene. Results are discussed as indicating a constitutive growth factor independent activation of growth factor signal transduction by the activated Ha-ras.
Maly
K
K
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Oberhuber
H
H
Doppler
W
W
Hoflacher
J
J
Jaggi
R
R
Groner
B
B
Grunicke
H
H
D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D011905:Genes, ras; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D017923:Sodium-Hydrogen Exchangers; D014162:Transfection
D002352:Carrier Proteins; D006133:Growth Substances; D007295:Inositol Phosphates; C000715470:MAS1 protein, human; D010716:Phosphatidylinositols; D000090063:Proto-Oncogene Mas; D017923:Sodium-Hydrogen Exchangers; D002118:Calcium