Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species
Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species
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DOI：
10.1073/pnas.1011665108
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发表时间：
2011-06-28
影响因子：
11.1
通讯作者：
Furdui, Cristina M.
中科院分区：
文献类型：
--
作者：
Wani, Revati;Qian, Jiang;Furdui, Cristina M.
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.
