Aurora A regulation by reversible cysteine oxidation reveals evolutionarily conserved redox control of Ser/Thr protein kinase activity

Byrne, Dominic P, Shrestha, Safal, Galler, Martin, Cao, Min, Daly, Leonard A ORCID: 0000-0001-9712-9676, Campbell, Amy E ORCID: 0000-0001-8390-4360, Eyers, Claire E ORCID: 0000-0002-3223-5926, Veal, Elizabeth A, Kannan, Natarajan and Eyers, Patrick A ORCID: 0000-0002-9220-2966 (2020) Aurora A regulation by reversible cysteine oxidation reveals evolutionarily conserved redox control of Ser/Thr protein kinase activity. Science Signaling, 13 (639). eaax2713-.

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Official URL: https://stke.sciencemag.org/content/13/639/eaax271...

Abstract

Reactive oxygen species (ROS) are physiological mediators of cellular signaling and play potentially damaging roles in human diseases. In this study, we found that the catalytic activity of the Ser/Thr kinase Aurora A was inhibited by the oxidation of a conserved cysteine residue (Cys290) that lies adjacent to Thr288, a critical phosphorylation site in the activation segment. Cys is present at the equivalent position in ~100 human Ser/Thr kinases, a residue that we found was important not only for the activity of human Aurora A but also for that of fission yeast MAPK-activated kinase (Srk1) and PKA (Pka1). Moreover, the presence of this conserved Cys predicted biochemical redox sensitivity among a cohort of human CAMK, AGC, and AGC-like kinases. Thus, we predict that redox modulation of the conserved Cys290 of Aurora A may be an underappreciated regulatory mechanism that is widespread in eukaryotic Ser/Thr kinases. Given the key biological roles of these enzymes, these findings have implications for understanding physiological and pathological responses to ROS and highlight the importance of protein kinase regulation through multivalent modification of the activation segment.

Item Type:	Article
Uncontrolled Keywords:	Hela Cells, Animals, Humans, Mice, Cysteine, Evolution, Molecular, Oxidation-Reduction, Aurora Kinase A
Depositing User:	Symplectic Admin
Date Deposited:	18 Aug 2020 10:34
Last Modified:	18 Jan 2023 23:37
DOI:	10.1126/scisignal.aax2713
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3097996