Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.freeradbiomed.2007.01.013
DC FieldValue
dc.titlePhosphorylation of the survival kinase Akt by superoxide is dependent on an ascorbate-reversible oxidation of PTEN
dc.contributor.authorLim, S.
dc.contributor.authorClement, M.-V.
dc.date.accessioned2011-11-29T05:57:37Z
dc.date.available2011-11-29T05:57:37Z
dc.date.issued2007
dc.identifier.citationLim, S., Clement, M.-V. (2007). Phosphorylation of the survival kinase Akt by superoxide is dependent on an ascorbate-reversible oxidation of PTEN. Free Radical Biology and Medicine 42 (8) : 1178-1192. ScholarBank@NUS Repository. https://doi.org/10.1016/j.freeradbiomed.2007.01.013
dc.identifier.issn08915849
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/28635
dc.description.abstractIn this report, we demonstrate that in serum-deprived mouse embryonic fibroblasts an increase in intracellular level of superoxide through pharmacological inhibition of the Cu/ZnSOD protein or the down-regulation of its expression using specific siRNA mimics growth factor-induced phosphorylation of Akt. Using the PI3K inhibitor LY294002 and PTEN knockout mouse embryonic fibroblasts, we show that phosphorylation of Akt by superoxide requires the production of PIP3 and that the target for the induction of Akt phosphorylation by O2{radical dot}- is the phosphatase PTEN. Interestingly, the inhibition of PTEN involves an O2{radical dot}--mediated oxidation of the phosphatase rather than regulation of its phosphorylation or decreased protein expression. Moreover, using differential reduction of oxidized protein by DTT and ascorbate, O2{radical dot}--dependent oxidation of PTEN is shown to be due to S-nitrosylation of the protein. Finally, exposure of serum-deprived mouse embryonic fibroblasts to fetal bovine serum leads to a rapid and strong phosphorylation of Akt that is dependent on an ascorbate-reversible O2{radical dot}--mediated oxidation of PTEN. These results support O2{radical dot}- as a physiologically relevant second messenger for Akt activation through S-nitrosylation of PTEN and offer a mechanistic explanation for the mitogenic and prosurvival activities of O2{radical dot}-. © 2007 Elsevier Inc. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.freeradbiomed.2007.01.013
dc.sourceScopus
dc.subjectAkt
dc.subjectFree radicals
dc.subjectPTEN
dc.subjectS-nitrosylation
dc.subjectSuperoxide
dc.typeArticle
dc.contributor.departmentBIOCHEMISTRY
dc.description.doi10.1016/j.freeradbiomed.2007.01.013
dc.description.sourcetitleFree Radical Biology and Medicine
dc.description.volume42
dc.description.issue8
dc.description.page1178-1192
dc.description.codenFRBME
dc.identifier.isiut000245514000006
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