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Publication : Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species.

First Author  Wani R Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  26 Pages  10550-5
PubMed ID  21670275 Mgi Jnum  J:173552
Mgi Id  MGI:5014444 Doi  10.1073/pnas.1011665108
Citation  Wani R, et al. (2011) Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species. Proc Natl Acad Sci U S A 108(26):10550-5
abstractText  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.
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