title: Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species.
abstract: Isoform-specific signaling of Akt, a major signaling hub and a prominent therapeutic target, remained poorly defined until recently. Subcellular distribution, tissue-specific expression, substrate specificity, and posttranslational modifications are believed to underlie isoform-specific signaling of Akt. The studies reported here show inhibition of Akt2 activity under physiologically relevant conditions of oxidation created by PDGF-induced reactive oxygen species. Combined MS and functional assays identified Cys124 located in the linker region between the N-terminal pleckstrin homology domain and the catalytic kinase domain as one of the unique regulatory redox sites in Akt2 with functional consequence on PDGF-stimulated glucose uptake. A model is proposed describing the consequence of increased endogenous oxidation induced by extracellular cues such as PDGF on Akt2 activity.
authors.affiliation: Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27109, USA.
authors.forename: Revati
authors.initials: R
authors.lastname: Wani
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.forename: Leimiao
authors.initials: L
authors.lastname: Yin
authors.forename: Erika
authors.initials: E
authors.lastname: Bechtold
authors.forename: S Bruce
authors.initials: SB
authors.lastname: King
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Poole
authors.forename: Eunok
authors.initials: E
authors.lastname: Paek
authors.forename: Allen W
authors.initials: AW
authors.lastname: Tsang
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Furdui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D051966:Phospholipase C gamma / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma