ArticleThe Journal of biological chemistry2012
Direct binding and regulation of RhoA protein by cyclic GMP-dependent protein kinase Iα.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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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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
34 citing papers in PubMed, 51 citations in OpenAlex.
- Unresolved mechanisms: a hypothesized spatial regulation of myosin light chain phosphorylation within the walls of resistance arteries.Frontiers in physiology · 2026Article
- CO and NO Coordinate Developmental Neuron Migration.International journal of molecular sciences · 2025Article
- A Novel Single-Color FRET Sensor for Rho-Kinase Reveals Calcium-Dependent Activation of RhoA and ROCK.Sensors (Basel, Switzerland) · 2024Article
- MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms.JCI insight · 2021Article
- Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4).International journal of molecular sciences · 2021Article
- A substitution in cGMP-dependent protein kinase 1 associated with aortic disease induces an active conformation in the absence of cGMP.The Journal of biological chemistry · 2020Article
- The Role of Nitric Oxide in Regulating Intestinal Redox Status and Intestinal Epithelial Cell Functionality.International journal of molecular sciences · 2019Review
- Oxidation of cysteine 117 stimulates constitutive activation of the type Iα cGMP-dependent protein kinase.The Journal of biological chemistry · 2018Article
- Regulation of RhoA GTPase and various transcription factors in the RhoA pathway.Journal of cellular physiology · 2018Review
- An N-terminally truncated form of cyclic GMP-dependent protein kinase Iα (PKG Iα) is monomeric and autoinhibited and provides a model for activation.The Journal of biological chemistry · 2018Article
- The activity of cGMP-dependent protein kinase Iα is not directly regulated by oxidation-induced disulfide formation at cysteine 43.The Journal of biological chemistry · 2017Article
- Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability.Circulation research · 2017Review
- Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response.Nature communications · 2016Article
- Phosphodiesterase 5 Inhibition Limits Doxorubicin-induced Heart Failure by Attenuating Protein Kinase G Iα Oxidation.The Journal of biological chemistry · 2016Article
- Old dog, new tricks: novel cardiac targets and stress regulation by protein kinase G.Cardiovascular research · 2016Review
- Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Lycopene Ameliorates Transplant Arteriosclerosis in Vascular Allograft Transplantation by Regulating the NO/cGMP Pathways and Rho-Associated Kinases Expression.Oxidative medicine and cellular longevity · 2016Article
- Molecular Screen Identifies Cardiac Myosin-Binding Protein-C as a Protein Kinase G-Iα Substrate.Circulation. Heart failure · 2015Article
- GRP78/Dna K Is a Target for Nexavar/Stivarga/Votrient in the Treatment of Human Malignancies, Viral Infections and Bacterial Diseases.Journal of cellular physiology · 2015Article
- Tadalafil attenuates graft arteriosclerosis of aortic transplant in a rat model.Iranian journal of basic medical sciences · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular smooth muscle cell (VSMC) tone is regulated by the state of myosin light chain (MLC) phosphorylation, which is in turn regulated by the balance between MLC kinase and MLC phosphatase (MLCP) activities. RhoA activates Rho kinase, which phosphorylates the regulatory subunit of MLC phosphatase, thereby inhibiting MLC phosphatase activity and increasing contraction and vascular tone. Nitric oxide is an important mediator of VSMC relaxation and vasodilation, which acts by increasing cyclic GMP (cGMP) levels in VSMC, thereby activating cGMP-dependent protein kinase Iα (PKGIα). PKGI is known to phosphorylate Rho kinase, preventing Rho-mediated inhibition of MLC phosphatase, promoting vasorelaxation, although the molecular mechanisms that mediate this are unclear. Here we identify RhoA as a target of activated PKGIα and show further that PKGIα binds directly to RhoA, inhibiting its activation and translocation. In protein pulldown and immunoprecipitation experiments, binding of RhoA and PKGIα was demonstrated via a direct interaction between the amino terminus of RhoA (residues 1-44), containing the switch I domain of RhoA, and the amino terminus of PKGIα (residues 1-59), which includes a leucine zipper heptad repeat motif. Affinity assays using cGMP-immobilized agarose showed that only activated PKGIα binds RhoA, and a leucine zipper mutant PKGIα was unable to bind RhoA even if activated. Furthermore, a catalytically inactive mutant of PKGIα bound RhoA but did not prevent RhoA activation and translocation. Collectively, these results support that RhoA is a PKGIα target and that direct binding of activated PKGIα to RhoA is central to cGMP-mediated inhibition of the VSMC Rho kinase contractile pathway.
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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.