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.
CITATION STYLE
Wani, R., Qian, J., Yin, L., Bechtold, E., King, S. B., Poole, L. B., … Furdui, C. M. (2011). Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species. Proceedings of the National Academy of Sciences of the United States of America, 108(26), 10550–10555. https://doi.org/10.1073/pnas.1011665108
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