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

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...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-06, Vol.108 (26), p.10550-10555
Main Authors: Wani, Revati, Qian, Jiang, Yin, Leimiao, Bechtold, Erika, King, S. Bruce, Poole, Leslie B, Paek, Eunok, Tsang, Allen W, Furdui, Cristina M
Format: Article
Language:English
Subjects:
3T3 cells
active sites
Amino Acid Sequence
Animals
Base Sequence
Biological Sciences
Cell Line
Cells
Disulfides
DNA Primers
Glucose
Humans
Insulin
Kinases
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
NIH 3T3 Cells
Oxidation
Oxidation-Reduction
Phospholipase C gamma - metabolism
Phosphorylation
Physiological regulation
Platelet-Derived Growth Factor - metabolism
pleckstrin
post-translational modification
Protein isoforms
Protein Isoforms - metabolism
Proto-Oncogene Proteins c-akt - chemistry
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Reactive oxygen species
Reactive Oxygen Species - metabolism
sequence homology
Signal Transduction
Signaling proteins
substrate specificity
Tissues
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1011665108