Isozyme-specific posttranslational regulation fine-tunes signaling events. However, functional redundancy renders links between isozyme-specific modifications and downstream activities uncertain. Methods to study this phenomenon are underdeveloped. A redox-targeting-screen unveiled Akt3 as a first-responding isozyme sensing native electrophilic lipids. Electrophilic modification of Akt3 modulated downstream pathway responses in cells and zebrafish and markedly differed from Akt2-specific oxidative regulation. The study documents isozyme-specific and chemical-redox-signal-personalized physiologic responses, promising precision therapeutic discrimination.

Privileged First-Responding redox sensors in isozyme-specific apoptosis regulation

253rd National Meeting (2017)

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