Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor

Phosphatidylinositol S-kinase mediates several actions of insulin including its antilipolytic effect. This effect is elicited by the insulin-stimulate d serine phosphorylation and activation of cGMP-inhibited phosphodiesterase (PDE3B). In human adipocytes, we found that insulin differentially stimula ted phosphatidylinositol S-kinase activity; the lipid kinase activity was a ssociated with IRS-1, whereas the serine kinase activity was associated wit h the insulin receptor and phosphorylated a number of proteins including p8 5, p110, and a 135-kDa protein identified as PDE3B. PDE3B phosphorylation w as associated with enzyme activation, thus initiating the antilipolytic eff ect of insulin. These results show a novel pathway for intracellular signal ing through the insulin receptor leading to the serine phosphorylation of k ey proteins involved in insulin action.