Cysteine redox sensor in PKGIα enables oxidant-induced activation

Joseph R. Burgoyne, Melanie Madhani, Friederike Cuello, Rebecca L. Charles, Jonathan P. Brennan, Ewald Schröder, Darren D. Browning, Philip Eaton

Research output: Contribution to journalArticle

332 Scopus citations

Abstract

Changes in the concentration of oxidants in cells can regulate biochemical signaling mechanisms that control cell function. We have found that guanosine 3′,5′-monophosphate (cGMP) - dependent protein kinase (PKG) functions directly as a redox sensor. The Iα isoform, PKGIα, formed an interprotein disulfide linking its two subunits in cells exposed to exogenous hydrogen peroxide. This oxidation directly activated the kinase in vitro, and in rat cells and tissues. The affinity of the kinase for substrates it phosphorylates was enhanced by disulfide formation. This oxidation-induced activation represents an alternate mechanism for regulation along with the classical activation involving nitric oxide and cGMP. This mechanism underlies cGMP-independent vasorelaxation in response to oxidants in the cardiovascular system and provides a molecular explanation for how hydrogen peroxide can operate as an endothelium-derived hyperpolarizing factor.

Original languageEnglish (US)
Pages (from-to)1393-1397
Number of pages5
JournalScience
Volume317
Issue number5843
DOIs
StatePublished - Sep 7 2007

ASJC Scopus subject areas

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    Burgoyne, J. R., Madhani, M., Cuello, F., Charles, R. L., Brennan, J. P., Schröder, E., Browning, D. D., & Eaton, P. (2007). Cysteine redox sensor in PKGIα enables oxidant-induced activation. Science, 317(5843), 1393-1397. https://doi.org/10.1126/science.1144318