ArticleMolecular pharmacology2012
Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 33 citations in OpenAlex.
- Discovery of RGS2-FBXO44 interaction inhibitors using a cell-based NanoBit assay.Molecular pharmacology · 2025Article
- A Phenotypic High-Throughput Screen Identifies Small Molecule Modulators of Endogenous RGS10 in BV-2 Cells.Journal of medicinal chemistry · 2024Article
- Article
- Regulator of G protein signaling 2 inhibits GαThe Journal of biological chemistry · 2022Article
- The Antipsychotic Drug Clozapine Suppresses the RGS4 Polyubiquitylation and Proteasomal Degradation Mediated by the Arg/N-Degron Pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.The Journal of biological chemistry · 2019Review
- Regulating the regulators: Epigenetic, transcriptional, and post-translational regulation of RGS proteins.Cellular signalling · 2018Review
- Proteolytic degradation of regulator of G protein signaling 2 facilitates temporal regulation of GThe Journal of biological chemistry · 2017Article
- The evolution of regulators of G protein signalling proteins as drug targets - 20 years in the making: IUPHAR Review 21.British journal of pharmacology · 2017Review
- Regulator of G Protein Signaling 10 (Rgs10) Expression Is Transcriptionally Silenced in Activated Microglia by Histone Deacetylase Activity.Molecular pharmacology · 2017Article
- Regulator of G Protein Signaling 6 Protects the Heart from Ischemic Injury.The Journal of pharmacology and experimental therapeutics · 2017Article
- Digoxin-Mediated Upregulation of RGS2 Protein Protects against Cardiac Injury.The Journal of pharmacology and experimental therapeutics · 2016Article
- Regulation of Cardiac Remodeling by Cardiac Na(+)/K(+)-ATPase Isoforms.Frontiers in physiology · 2016Review
- FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex.PloS one · 2015Article
- Identification of protein kinase C activation as a novel mechanism for RGS2 protein upregulation through phenotypic screening of natural product extracts.Molecular pharmacology · 2014Article
- Functional role, mechanisms of regulation, and therapeutic potential of regulator of G protein signaling 2 in the heart.Trends in cardiovascular medicine · 2014Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Regulator of G protein signaling 2 (RGS2), a G(q)-specific GTPase-activating protein, is strongly implicated in cardiovascular function. RGS2(-/-) mice are hypertensive and prone to heart failure, and several rare human mutations that accelerate RGS2 degradation have been identified among patients with hypertension. Therefore, pharmacological up-regulation of RGS2 protein levels might be beneficial. We used a β-galactosidase complementation method to screen several thousand compounds with known pharmacological functions for those that increased RGS2 protein levels. Several cardiotonic steroids (CTSs), including ouabain and digoxin, increased RGS2 but not RGS4 protein levels. CTSs increased RGS2 protein levels through a post-transcriptional mechanism, by slowing protein degradation. RGS2 mRNA levels in primary vascular smooth muscle cells were unaffected by CTS treatment, whereas protein levels were increased 2- to 3-fold. Na(+)/K(+)-ATPase was required for the increase in RGS2 protein levels, because the effect was lost in Na(+)/K(+)-ATPase-knockdown cells. Furthermore, we demonstrated that CTS-induced increases in RGS2 levels were functional and reduced receptor-stimulated, G(q)-dependent, extracellular signal-regulated kinase phosphorylation. Finally, we showed that in vivo treatment with digoxin led to increased RGS2 protein levels in heart and kidney. CTS-induced increases in RGS2 protein levels and function might modify several deleterious mechanisms in hypertension and heart failure. This novel CTS mechanism might contribute to the beneficial actions of low-dose digoxin treatment in heart failure. Our results support the concept of small-molecule modulation of RGS2 protein levels as a new strategy for cardiovascular therapy.
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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.