ArticleArteriosclerosis, thrombosis, and vascular biology2008
Protein kinase G phosphorylates soluble guanylyl cyclase on serine 64 and inhibits its activity.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Challenging the Norm: The Unrecognized Impact of Soluble Guanylyl Cyclase Subunits in Cancer.International journal of molecular sciences · 2024Review
- Per-ARNT-Sim Domains in Nitric Oxide Signaling by Soluble Guanylyl Cyclase.Journal of molecular biology · 2024Review
- New Therapeutics for Heart Failure: Focusing on cGMP Signaling.International journal of molecular sciences · 2023Review
- Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase.Cells · 2023Review
- The Interplay between cGMP and Calcium Signaling in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Article
- Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease.Scientific reports · 2020Article
- Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure.Scientific reports · 2019Article
- The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats.Scientific reports · 2018Article
- Redox regulation of soluble guanylyl cyclase.Nitric oxide : biology and chemistry · 2018Review
- Structure and Activation of Soluble Guanylyl Cyclase, the Nitric Oxide Sensor.Antioxidants & redox signaling · 2017Review
- Cytokine-induced S-nitrosylation of soluble guanylyl cyclase and expression of phosphodiesterase 1A contribute to dysfunction of longitudinal smooth muscle relaxation.The Journal of pharmacology and experimental therapeutics · 2015Article
- Nitrergic neuromuscular transmission in the mouse internal anal sphincter is accomplished by multiple pathways and postjunctional effector cells.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.PLoS biology · 2014Article
- Regulation of soluble guanylate cyclase by matricellular thrombospondins: implications for blood flow.Frontiers in physiology · 2014Review
- Molecular model of a soluble guanylyl cyclase fragment determined by small-angle X-ray scattering and chemical cross-linking.Biochemistry · 2013Article
- Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I): pathophysiological significance.Cardiovascular research · 2013Review
- Systems biology of HBOC-induced vasoconstriction.Current drug discovery technologies · 2012Review
- Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model.American journal of physiology. Heart and circulatory physiology · 2012Article
- Dynamic ligand exchange in soluble guanylyl cyclase (sGC): implications for sGC regulation and desensitization.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveBinding of nitric oxide (NO) to soluble guanylyl cyclase (sGC) leads to increased cGMP synthesis that activates cGMP-dependent protein kinase (PKG). Herein, we tested whether sGC activity is regulated by PKG. METHODS AND
resultsOverexpression of a constitutively active form of PKG (DeltaPKG) stimulated (32)P incorporation into the alpha1 subunit. Serine to alanine mutation of putative sites revealed that Ser64 is the main phosphorylation site for PKG. Using a phospho-specific antibody we observed that endogenous sGC phosphorylation on Ser 64 increases in cells and tissues exposed to NO, in a PKG-inhibitable manner. Wild-type (wt) sGC coexpressed with DeltaPKG exhibited lower basal and NO-stimulated cGMP accumulation, whereas the S64A alpha1/beta1 sGC was resistant to the PKG-induced reduction in activity. Using purified sGC we observed that the S64D alpha1 phosphomimetic /beta1 dimer exhibited lower Vmax; moreover, the decrease in Km after NO stimulation was less pronounced in S64D alpha1/beta1 compared to wild-type sGC. Expression of a phosphorylation-deficient sGC showed enhanced responsiveness to endothelium-derived NO, reduced desensitization to acute NO exposure, and allowed for greater VASP phosphorylation.
conclusionsWe conclude that PKG phosphorylates sGC on Ser64 of the alpha1 subunit and that phosphorylation inhibits sGC activity, establishing a negative feedback loop.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.