title: Redox control of cytosolic Akt phosphorylation in PTEN null cells.
abstract: This article demonstrates a role for intracellular reactive oxygen species in the hyperphosphorylation of Akt in cells that have lost the expression of the tumor suppressor PTEN. Using mouse embryonic fibroblasts in which the expression of PTEN was knocked out, we show that a decrease in intracellular superoxide anion resulted in a rapid dephosphorylation of Akt at Thr308 followed by Ser473. Whereas dephosphorylation was detected in the cytosolic pool of Akt, phosphorylation of the membrane pool of the kinase remained unaffected. Dephosphorylation of cytosolic Akt was attributed to an increase in the interaction between Akt and the catalytic subunit of the protein phosphatase PP2A, which correlated with an increase in the amount of the oxidized versus the reduced form of the kinase. These results were corroborated in the PTEN knockout prostate cancer cell line LNCaP and in the melanoma cell line M14 stably transfected with a constitutively active form of Rac1.
authors.affiliation: Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Singapore.
authors.forename: Le
authors.initials: L
authors.lastname: Luo
authors.forename: Jaspal
authors.initials: J
authors.lastname: Kaur Kumar
authors.forename: Marie-Véronique
authors.initials: MV
authors.lastname: Clément
mesh_terms: D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000201:enzymology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D010766:Phosphorylation; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D009861:Onium Compounds; D013481:Superoxides; C007517:diphenyleneiodonium; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D054648:Protein Phosphatase 2; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse