The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate is mitogenic for normal chicken embryo fibroblasts and also causes these cells to express transiently many properties of cells transformed by Rous sarcoma virus. Since some mitogenic hormones stimulate a tyrosine-specific protein kinase activity, and since the transforming protein of RSV is a tyrosine-specific protein kinase, we have examined whether TPA also stimulates protein phosphorylation on tyrosine. We report here that TPA treatment of normal cells resulted in a very rapid phosphorylation on tyrosine of a protein peak of Mr 40 to 43 kilodaltons. Thus, a similar biochemical activity (tyrosine phosphorylation) is associated with the action of polypeptide mitogenic hormones, Rous sarcoma virus and a tumor promoter. In addition, TPA treatment resulted in rapid changes in phosphorylation of proteins on serine and threonine.
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