Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor.
Phosphatidylinositol 3-kinase mediates several actions of insulin including its antilipolytic effect. This effect is elicited by the insulin-stimulated serine phosphorylation and activation of cGMP-inhibited phosphodiesterase (PDE3B). In human adipocytes, we found that insulin differentially stimulated phosphatidylinositol 3-kinase activity; the lipid kinase activity was associated with IRS-1, whereas the serine kinase activity was associated with the insulin receptor and phosphorylated a number of proteins including p85, p110, and a 135-kDa protein identified as PDE3B. PDE3B phosphorylation was associated with enzyme activation, thus initiating the antilipolytic effect of insulin. These results show a novel pathway for intracellular signaling through the insulin receptor leading to the serine phosphorylation of key proteins involved in insulin action.
Rondinone
C M
CM
Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Goteborg University, Sahlgrenska University Hospital, Goteborg S-413 45, Sweden.
Carvalho
E
E
Rahn
T
T
Manganiello
V C
VC
Degerman
E
E
Smith
U P
UP
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000302:isolation & purification / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004789:Enzyme Activation; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins; D008970:Molecular Weight; D019869:Phosphatidylinositol 3-Kinases / Q000302:isolation & purification / Q000378:metabolism*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011972:Receptor, Insulin; C526292:IRS1 protein, human; C517291:PDE3B protein, human