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. |