Ha-Ras stimulates uptake and phosphorylation of ethanolamine: inhibition by wortmannin.
Transformation of NIH 3T3 fibroblasts by Ha-Ras resulted in large increases in the phosphorylation of both [14C]ethanolamine (Etn) and [14C]choline (Cho) when these precursors were added to the medium. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), preferentially decreased phosphorylation of externally added Etn in the Ha-Ras transformed, but not in the untransformed, fibroblasts. However, wortmannin had no effect on the phosphorylation of Etn formed endogenously by phorbol ester-stimulated hydrolysis of phosphatidylethanolamine. Data suggest that interaction of mutated Ras with PI3K leads to specific stimulation of Etn uptake, followed by nearly quantitative phosphorylation of Etn by a Ras-activated Cho/Etn kinase.
Hormel Institute, University of Minnesota, Austin 55912.
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D016475:3T3 Cells; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002461:Cell Line, Transformed; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism*; D011905:Genes, ras; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D000077191:Wortmannin
D000730:Androstadienes; D004983:Ethanolamines; D019856:Ethanolamine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000077191:Wortmannin