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

• DOI: 10.1073/pnas.1011665108
• Publication Date: 2011-06-14T18:03:48Z
• Authors: Revati Wani; Jiang Qian; Leimiao Yin; Erika Bechtold; S. Bruce King; Leslie B. Poole; Eunok Paek; Allen W. Tsang; Cristina M. Furdui
• Keywords: Pleckstrin homology domain; AKT2; Proto-Oncogene Proteins c-akt

Isoform-specific signaling of Akt, a major hub and prominent therapeutic target, remained poorly defined until recently. Subcellular distribution, tissue-specific expression, substrate specificity, posttranslational modifications are believed to underlie isoform-specific Akt. The studies reported here show inhibition Akt2 activity under physiologically relevant conditions oxidation created by PDGF-induced reactive oxygen species. Combined MS functional assays identified Cys124 located in the linker region between N-terminal pleckstrin homology domain catalytic kinase as one unique regulatory redox sites with consequence on PDGF-stimulated glucose uptake. A model is proposed describing increased endogenous induced extracellular cues such PDGF activity.