PUBLICATION
Akt3 is a privileged first responder in isozyme-specific electrophile response
- Authors
- Long, M.J., Parvez, S., Zhao, Y., Surya, S.L., Wang, Y., Zhang, S., Aye, Y.
- ID
- ZDB-PUB-170124-1
- Date
- 2017
- Source
- Nature Chemical Biology 13(3): 333-338 (Journal)
- Registered Authors
- Aye, Yimon
- Keywords
- none
- MeSH Terms
-
- HEK293 Cells
- Humans
- Isoenzymes/metabolism
- Lipids
- Oxidation-Reduction
- Phenotype
- Proto-Oncogene Proteins c-akt/genetics
- Proto-Oncogene Proteins c-akt/metabolism*
- PubMed
- 28114274 Full text @ Nat. Chem. Biol.
Citation
Long, M.J., Parvez, S., Zhao, Y., Surya, S.L., Wang, Y., Zhang, S., Aye, Y. (2017) Akt3 is a privileged first responder in isozyme-specific electrophile response. Nature Chemical Biology. 13(3):333-338.
Abstract
Isozyme-specific post-translational regulation fine tunes signaling events. However, redundancy in sequence or activity renders links between isozyme-specific modifications and downstream functions uncertain. Methods to study this phenomenon are underdeveloped. Here we use a redox-targeting screen to reveal that Akt3 is a first-responding isozyme sensing native electrophilic lipids. Electrophile modification of Akt3 modulated downstream pathway responses in cells and Danio rerio (zebrafish) and markedly differed from Akt2-specific oxidative regulation. Digest MS sequencing identified Akt3 C119 as the privileged cysteine that senses 4-hydroxynonenal. A C119S Akt3 mutant was hypomorphic for all downstream phenotypes shown by wild-type Akt3. This study documents isozyme-specific and chemical redox signal-personalized physiological responses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping