Wortmannin inhibits carcinogen-stimulated phosphorylation of ethanolamine and choline.
We have previously reported that in C3H/10T1/2 fibroblasts the environmental carcinogen 7,12-dimethyl-benz[a]anthracene (DMBA) stimulated phosphorylation of ethanolamine (Etn). Here we show that in these fibroblasts DMBA also stimulates phosphorylation of choline (Cho). Wortmannin (50-200 nM), an established inhibitor of phosphatidylinositol-3-kinase (PI3K), significantly inhibited DMBA-induced phosphorylation of both Etn and Cho. Wortmannin also inhibited the effect of insulin, a major activator of PI3K, on DNA synthesis. However, insulin had no effect on the phosphorylation of Etn and Cho. These data suggest that a carcinogen-induced kinase phosphorylates both Etn and Cho, and that the inhibitory effect of wortmannin on Etn/Cho kinase activity may be unrelated to its inhibitory effect on PI3K activity.
Hormel Institute, University of Minnesota, Austin 55912.
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D016475:3T3 Cells; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism*; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D000077191:Wortmannin
D000730:Androstadienes; D002273:Carcinogens; D004983:Ethanolamines; D015127:9,10-Dimethyl-1,2-benzanthracene; D019856:Ethanolamine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D002794:Choline; D000077191:Wortmannin