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.