Evidence map›Paper›PMID 24106280›Full record

ArticleThe Journal of biological chemistry2013

Agonist-induced Ca2+ sensitization in smooth muscle: redundancy of Rho guanine nucleotide exchange factors (RhoGEFs) and response kinetics, a caged compound study.

Mykhaylo V Artamonov, Ko Momotani, Andra Stevenson, David R Trentham, Urszula Derewenda, Zygmunt S Derewenda, Paul W Read, J Silvio Gutkind, Avril V Somlyo

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Involvement of inhibitor kappa B kinase 2 (IKK2) in the regulation of vascular tone.Laboratory investigation; a journal of technical methods and pathology · 2018
    Article
  7. Article
  8. Review
  9. Article
  10. Chronic hypoxia alters fetal cerebrovascular responses to endothelin-1.American journal of physiology. Cell physiology · 2017
    Article
  11. Review
  12. Article
  13. Article
  14. Article
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  17. Review
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Mykhaylo V ArtamonovDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908.
Ko MomotaniDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908.
Andra StevensonDepartment of Cardiovascular Diseases, Merck Research Laboratories, Kenilworth, New Jersey 07033.
David R TrenthamThe Randall Division of Cell and Molecular Biophysics, School of Biomedical Sciences, King's College London, London SE1 1UK, United Kingdom.
Urszula DerewendaDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908.
Zygmunt S DerewendaDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908.
Paul W ReadDepartment of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908.
J Silvio GutkindOral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892.
Avril V SomlyoDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908. Electronic address: avs5u@virginia.edu.
University of Virginia · USKing's College London · GBMerck & Co., Inc., Rahway, NJ, USA (United States) · USNational Institutes of Health · US

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Thomas P. Loughran · 1987 to 2026
$72.1M
Molecular Mechanisms Of Growth Control And CarcinogenesisZIADE000551 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI GUTKIND, JORGE SILVIO · 2009 to 2015
$11.5M
Molecular Mechanisms of RhoA-mediated Ca2+Sensitization in Vascular Smooth MuscleR01GM086457 · NIGMS · UNIVERSITY OF VIRGINIA · PI DEREWENDA, URSZULA, DEREWENDA, ZYGMUNT S · 2009 to 2017
$5.4M
Myosin phosphatase autoinhibition in gastrointestinal smooth muscle contractionR01DK088905 · NIDDK · UNIVERSITY OF VIRGINIA · PI ETO, MASUMI, SOMLYO, AVRIL V. · 2010 to 2012
$1.1M
NCI NIH HHS P30 CA044579NIDDK NIH HHS R01 DK088905NIDDK NIH HHS R01DK088905NIGMS NIH HHS GM086457NIGMS NIH HHS R01 GM086457
6 · The paper itself

Abstract

Many agonists, acting through G-protein-coupled receptors and Gα subunits of the heterotrimeric G-proteins, induce contraction of smooth muscle through an increase of [Ca(2+)]i as well as activation of the RhoA/RhoA-activated kinase pathway that amplifies the contractile force, a phenomenon known as Ca(2+) sensitization. Gα12/13 subunits are known to activate the regulator of G-protein signaling-like family of guanine nucleotide exchange factors (RhoGEFs), which includes PDZ-RhoGEF (PRG) and leukemia-associated RhoGEF (LARG). However, their contributions to Ca(2+)-sensitized force are not well understood. Using permeabilized blood vessels from PRG(-/-) mice and a new method to silence LARG in organ-cultured blood vessels, we show that both RhoGEFs are activated by the physiologically and pathophysiologically important thromboxane A2 and endothelin-1 receptors. The co-activation is the result of direct and independent activation of both RhoGEFs as well as their co-recruitment due to heterodimerization. The isolated recombinant C-terminal domain of PRG, which is responsible for heterodimerization with LARG, strongly inhibited Ca(2+)-sensitized force. We used photolysis of caged phenylephrine, caged guanosine 5'-O-(thiotriphosphate) (GTPγS) in solution, and caged GTPγS or caged GTP loaded on the RhoA·RhoGDI complex to show that the recruitment and activation of RhoGEFs is the cause of a significant time lag between the initial Ca(2+) transient and phasic force components and the onset of Ca(2+)-sensitized force.

Indexed as

AnimalsCalciumCell LineGene SilencingGuanine Nucleotide Exchange FactorsGuanosine 5'-O-(3-Thiotriphosphate)HumansMiceMice, KnockoutOrgan Culture TechniquesPhenylephrineProtein MultimerizationProtein Structure, TertiaryRabbitsRatsReceptor, Endothelin A1-(2-nitro)phenylethyl-P(3)-guanosine 5'-O-(3-thio)triphosphateARHGEF11 protein, humanARHGEF11 protein, mouseARHGEF12 protein, humanArhgef12 protein, mouseArhgef12 protein, ratCalciumGuanine Nucleotide Exchange FactorsGuanosine 5'-O-(3-Thiotriphosphate)N-2-nitrobenzylphenylephrinePDZ-RhoGEF, ratPhenylephrineReceptor, Endothelin AReceptors, Thromboxane A2, Prostaglandin H2Recombinant ProteinsrhoA GTP-Binding ProteinRHOA protein, humanRhoA protein, mouserho GTP-Binding ProteinsRho Guanine Nucleotide Exchange Factorsrho-Specific Guanine Nucleotide Dissociation InhibitorsCalciumGuanine Nucleotide Exchange Factor (GEF)RhoSignal TransductionSmooth Muscle

Identifiers

PMID24106280
PMCPMC3837142
OpenAlexW1977204598

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.