Evidence map›Paper›PMID 23760269›Full record

ArticleThe Journal of biological chemistry2013

Role of tyrosine phosphorylation in the muscarinic activation of the cystic fibrosis transmembrane conductance regulator (CFTR).

Arnaud Billet, Yishan Luo, Haouaria Balghi, John W Hanrahan

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 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023
    Pooled it
  2. Trial
  3. Potassium Channels of the Airway Epithelium.Acta physiologica (Oxford, England) · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Article
  9. Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024
    Review
  10. Article
  11. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport.American journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Increases in cytosolic CaCellular and molecular life sciences : CMLS · 2019
    Article
  17. Review
  18. Article
  19. Synergy of cAMP and calcium signaling pathways in CFTR regulation.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  20. Article
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

4 authors at 2 institutions in 1 country.

Arnaud BilletDepartment of Physiology, McGill University and Research Institute of the McGill University Hospital Centre, Montréal, Quebec H3G 1Y6, Canada. arnaud.billet@mcgill.ca
Yishan Luo
Haouaria Balghi
John W Hanrahan
McGill University · CAMcGill University Health Centre · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride (Cl(-)) channel, which plays an important role in physiological anion and fluid secretion, and is defective in several diseases. Although its activation by PKA and PKC has been studied extensively, its regulation by receptors is less well understood. To study signaling involved in CFTR activation, we measured whole-cell Cl(-) currents in BHK cells cotransfected with GPCRs and CFTR. In cells expressing the M3 muscarinic acetylcholine receptor, the agonist carbachol (Cch) caused strong activation of CFTR through two pathways; the canonical PKA-dependent mechanism and a second mechanism that involves tyrosine phosphorylation. The role of PKA was suggested by partial inhibition of cholinergic stimulation by the specific PKA inhibitor Rp-cAMPS. The role of tyrosine kinases was suggested by Cch stimulation of 15SA-CFTR and 9CA-CFTR, mutants that lack 15 PKA or 9 PKC consensus sequences and are unresponsive to PKA or PKC stimulation, respectively. Moreover the residual Cch response was sensitive to inhibitors of the Pyk2 and Src tyrosine kinase family. Our results suggest that tyrosine phosphorylation acts on CFTR directly and through inhibition of the phosphatase PP2A. Results suggest that PKA and tyrosine kinases contribute to CFTR regulation by GPCRs that are expressed at the apical membrane of intestinal and airway epithelia.

Indexed as

AnimalsBenzoatesCalciumCarbacholCell LineCholinergic AgonistsCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorEnzyme InhibitorsFocal Adhesion Kinase 2HumansImmunoblottingMembrane PotentialsMutationPatch-Clamp Techniques3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinoneadenosine-3',5'-cyclic phosphorothioateBenzoatesCalciumCarbacholCholinergic AgonistsCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorEnzyme InhibitorsFocal Adhesion Kinase 2Protein Phosphatase 2Receptor, Muscarinic M3src-Family KinasesThiazolidinesThionucleotidesTyrosineCFTRG Protein-coupled Receptors (GPCR)Muscarinic 3 ReceptorPP2ASrcTyrosine Protein Kinase (Tyrosine Kinase)

Identifiers

PMID23760269
PMCPMC3724638
OpenAlexW1967099368

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.