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

316 Citations (Scopus)

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

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Oxidants
Oxidation-Reduction
Cysteine
Disulfides
Hydrogen Peroxide
Phosphotransferases
Guanosine Monophosphate
Cyclic GMP-Dependent Protein Kinases
Cardiovascular System
Vasodilation
Endothelium
Nitric Oxide
Protein Isoforms

ASJC Scopus subject areas

  • General

Cite this

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

Cysteine redox sensor in PKGIα enables oxidant-induced activation. / Burgoyne, Joseph R.; Madhani, Melanie; Cuello, Friederike; Charles, Rebecca L.; Brennan, Jonathan P.; Schröder, Ewald; Browning, Darren D; Eaton, Philip.

In: Science, Vol. 317, No. 5843, 07.09.2007, p. 1393-1397.

Research output: Contribution to journalArticle

Burgoyne, JR, Madhani, M, Cuello, F, Charles, RL, Brennan, JP, Schröder, E, Browning, DD & Eaton, P 2007, 'Cysteine redox sensor in PKGIα enables oxidant-induced activation', Science, vol. 317, no. 5843, pp. 1393-1397. https://doi.org/10.1126/science.1144318
Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schröder E et al. Cysteine redox sensor in PKGIα enables oxidant-induced activation. Science. 2007 Sep 7;317(5843):1393-1397. https://doi.org/10.1126/science.1144318
Burgoyne, Joseph R. ; Madhani, Melanie ; Cuello, Friederike ; Charles, Rebecca L. ; Brennan, Jonathan P. ; Schröder, Ewald ; Browning, Darren D ; Eaton, Philip. / Cysteine redox sensor in PKGIα enables oxidant-induced activation. In: Science. 2007 ; Vol. 317, No. 5843. pp. 1393-1397.
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