ArticleThe Journal of biological chemistry2015
Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
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- A cryptic symmetry switch allosterically controls how the PF4 self-protein turns into a pathogenic antigen.Nature communications · 2026Article
- Aortic disease-linked mutations reveal unexpected convergent allosteric mechanisms of protein kinase G misregulation.Science advances · 2026Article
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- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Response of human metabolism to ultra-low and high nicotine cigarettes based on urine metabolomics and bioinformatic analysis.Tobacco induced diseases · 2024Article
- GNature communications · 2022Article
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- PDE-Mediated Cyclic Nucleotide Compartmentation in Vascular Smooth Muscle Cells: From Basic to a Clinical Perspective.Journal of cardiovascular development and disease · 2021Review
- Discovery of the First Non-cGMP Mimetic Small Molecule Activators of cGMP-Dependent Protein Kinase 1 α (PKG1α).ACS medicinal chemistry letters · 2021Article
- CHESPA/CHESCA-SPARKY: automated NMR data analysis plugins for SPARKY to map protein allostery.Bioinformatics (Oxford, England) · 2021Article
- TRIB2 modulates proteasome function to reduce ubiquitin stability and protect liver cancer cells against oxidative stress.Cell death & disease · 2021Article
- Signalling mechanisms in the cardiovascular protective effects of estrogen: With a focus on rapid/membrane signalling.Current research in physiology · 2021Review
- Keep a lid on it: A troika in kinase allostery.The Journal of biological chemistry · 2020Article
- Mechanism of allosteric inhibition in theThe Journal of biological chemistry · 2020Article
- Allosteric inhibition explained through conformational ensembles sampling distinct "mixed" states.Computational and structural biotechnology journal · 2020Review
- LncRNA EMX2OS, Regulated by TCF12, Interacts with FUS to Regulate the Proliferation, Migration and Invasion of Prostate Cancer Cells Through the cGMP-PKG Signaling Pathway.OncoTargets and therapy · 2020Article
- Exploring the structural basis of conformational heterogeneity and autoinhibition of human cGMP-specific protein kinase Iα through computational modelling and molecular dynamics simulations.Computational and structural biotechnology journal · 2020Article
- Dual Activities of Plant cGMP-Dependent Protein Kinase and Its Roles in Gibberellin Signaling and Salt Stress.The Plant cell · 2019Article
- Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Protein kinase G (PKG) is a major receptor of cGMP and controls signaling pathways often distinct from those regulated by cAMP. Hence, the selective activation of PKG by cGMP versus cAMP is critical. However, the mechanism of cGMP-versus-cAMP selectivity is only limitedly understood. Although the C-terminal cyclic nucleotide-binding domain B of PKG binds cGMP with higher affinity than cAMP, the intracellular concentrations of cAMP are typically higher than those of cGMP, suggesting that the cGMP-versus-cAMP selectivity of PKG is not controlled uniquely through affinities. Here, we show that cAMP is a partial agonist for PKG, and we elucidate the mechanism for cAMP partial agonism through the comparative NMR analysis of the apo, cGMP-, and cAMP-bound forms of the PKG cyclic nucleotide-binding domain B. We show that although cGMP activation is adequately explained by a two-state conformational selection model, the partial agonism of cAMP arises from the sampling of a third, partially autoinhibited state.
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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.