title: PTEN does not modulate GLUT4 translocation in rat adipose cells under physiological conditions.
abstract: PTEN is a 3'-inositol lipid phosphatase that dephosphorylates products of PI 3-kinase. Since PI 3-kinase is required for many metabolic actions of insulin, we investigated the role of PTEN in insulin-stimulated translocation of GLUT4. In control rat adipose cells, we observed a approximately 2-fold increase in cell surface GLUT4 upon maximal insulin stimulation. Overexpression of wild-type PTEN abolished this response to insulin. Translocation of GLUT4 in cells overexpressing PTEN mutants without lipid phosphatase activity was similar to that observed in control cells. Overexpression of PTEN-CBR3 (mutant with disrupted membrane association domain) partially impaired translocation of GLUT4. In Cos-7 cells, overexpression of wild-type PTEN had no effect on ERK2 phosphorylation in response to acute insulin stimulation. However, Elk-1 phosphorylation in response to chronic insulin treatment was significantly decreased. Thus, when PTEN is overexpressed, both its lipid phosphatase activity and subcellular localization play a role in antagonizing metabolic actions of insulin that are dependent on PI 3-kinase but independent of MAP kinase. However, because translocation of GLUT4 in cells overexpressing a dominant inhibitory PTEN mutant (C124S) was similar to that of control cells, we conclude that endogenous PTEN may not modulate metabolic functions of insulin under normal physiological conditions.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Mosser
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: M J
authors.initials: MJ
authors.lastname: Quon
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005799:Genes, Dominant / Q000235:genetics; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D009154:Mutation / Q000235:genetics; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1
chemical_list: D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; C494114:Elk1 protein, rat; D051275:Glucose Transporter Type 4; D007328:Insulin; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050807:ets-Domain Protein Elk-1; D019950:Mitogen-Activated Protein Kinase 1; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase