Choline phosphate and phorbol ester potentiate the mitogenic effect of insulin by competitive mechanisms in NIH 3T3...

Treatments of serum-starved NIH 3T3 fibroblasts with either 100 nM phorbol-12-myristate 13-acetate (PMA) or 1 mM choline phosphate (ChoP) greatly enhanced, in a mutually inhibitory manner, the stimulatory effect of insulin on DNA synthesis. Wortmannin and GF 109203X, inhibitors of phosphatidylinositol 3'-kinase and protein kinase C, respectively, inhibited only the combined mitogenic effects of PMA and insulin, but not that of ChoP and insulin. In the presence of 0.5% fetal calf serum, both ChoP and insulin, but not PMA, retained their mitogenic activities, while PMA abolished the stimulatory effect of insulin on DNA synthesis. The results indicate that PMA can both enhance and inhibit the mitogenic action of insulin, depending on the presence of serum factors and ChoP.