Tang, XiaoqingPowelka, Aimee M.Soriano, Neil A.Czech, Michael P.Guilherme, Adilson L.2022-08-232022-08-232005-04-132008-08-04J Biol Chem. 2005 Jun 10;280(23):22523-9. Epub 2005 Apr 11. <a href="http://dx.doi.org/10.1074/jbc.M501949200">Link to article on publisher's site</a>0021-9258 (Print)10.1074/jbc.M50194920015824124https://hdl.handle.net/20.500.14038/42329Glucose homeostasis is controlled by insulin in part through the stimulation of glucose transport in muscle and fat cells. This insulin signaling pathway requires phosphatidylinositol (PI) 3-kinase-mediated 3'-polyphosphoinositide generation and activation of Akt/protein kinase B. Previous experiments using dominant negative constructs and gene ablation in mice suggested that two phosphoinositide phosphatases, SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulate this insulin signaling pathway. Here we directly tested this hypothesis by selectively inhibiting the expression of SHIP2 or PTEN in intact cultured 3T3-L1 adipocytes through the use of short interfering RNA (siRNA). Attenuation of PTEN expression by RNAi markedly enhanced insulin-stimulated Akt and glycogen synthase kinase 3alpha (GSK-3alpha) phosphorylation, as well as deoxyglucose transport in 3T3-L1 adipocytes. In contrast, depletion of SHIP2 protein by about 90% surprisingly failed to modulate these insulin-regulated events under identical assay conditions. In control studies, no diminution of insulin signaling to the mitogen-activated protein kinases Erk1 and Erk2 was observed when either PTEN or SHIP2 were depleted. Taken together, these results demonstrate that endogenous PTEN functions as a suppressor of insulin signaling to glucose transport through the PI 3-kinase pathway in cultured 3T3-L1 adipocytes.en-US1-Phosphatidylinositol 3-Kinase3T3-L1 CellsAdipocytesAnimalsBiological TransportDeoxyglucoseDose-Response Relationship, DrugGene DeletionGene SilencingGlycogen Synthase Kinase 3HumansInsulinMAP Kinase Signaling SystemMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PTEN PhosphohydrolasePhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesPhosphorylationProtein Tyrosine PhosphatasesProtein-Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRNA InterferenceRNA, Small Interfering*Signal TransductionTime FactorsTumor Suppressor Proteinssrc Homology DomainsLife SciencesMedicine and Health SciencesJournal Articlehttps://escholarship.umassmed.edu/oapubs/689564499oapubs/689