Akt3 is a privileged first responder in isozyme-specific electrophile response

Marcus J.C. Long, Saba Parvez, Yi Zhao, Sanjna L. Surya, Yiran Wang, Sheng Zhang, Yimon Aye

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)333-338
Number of pages6
JournalNature Chemical Biology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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