Journal
SCIENCE
Volume 317, Issue 5843, Pages 1393-1397Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1144318
Keywords
-
Categories
Funding
- Medical Research Council [G0700320] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
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 I alpha isoform, PKGI alpha, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available