Evidence map›Paper›PMID 17581860›Full record

ArticleMolecular biology of the cell2007

The formation of the cAMP/protein kinase A-dependent annexin 2-S100A10 complex with cystic fibrosis conductance regulator protein (CFTR) regulates CFTR channel function.

Lee A Borthwick, Jean McGaw, Gregory Conner, Christopher J Taylor, Volker Gerke, Anil Mehta, Louise Robson, Richmond Muimo

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

29 citing papers in PubMed, 49 citations in OpenAlex.

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  7. TASK channels: channelopathies, trafficking, and receptor-mediated inhibition.Pflugers Archiv : European journal of physiology · 2020
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  8. Article
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  12. NM23 proteins: innocent bystanders or local energy boosters for CFTR?Laboratory investigation; a journal of technical methods and pathology · 2018
    Review
  13. Review
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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

8 authors at 5 institutions in 3 countries.

Lee A BorthwickAcademic Unit of Child Health, The University of Sheffield, Sheffield Children's Hospital, Sheffield, S10 2TH, United Kingdom.
Jean McGaw
Gregory Conner
Christopher J Taylor
Volker Gerke
Anil Mehta
Louise Robson
Richmond Muimo
Sheffield Children's Hospital · GBUniversity of Dundee · GBUniversity of Miami · USUniversity of Münster · DEUniversity of Sheffield · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein (CFTR), a cAMP/protein kinase A (PKA) and ATP-regulated Cl(-) channel. CFTR is increasingly recognized as a component of multiprotein complexes and although several inhibitory proteins to CFTR have been identified, protein complexes that stimulate CFTR function remain less well characterized. We report that annexin 2 (anx 2)-S100A10 forms a functional cAMP/PKA/calcineurin (CaN)-dependent complex with CFTR. Cell stimulation with forskolin/3-isobutyl-1-methylxanthine significantly increases the amount of anx 2-S100A10 that reciprocally coimmunoprecipitates with cell surface CFTR and calyculin A. Preinhibition with PKA or CaN inhibitors attenuates the interaction. Furthermore, we find that the acetylated peptide (STVHEILCKLSLEG, Ac1-14), but not the nonacetylated equivalent N1-14, corresponding to the S100A10 binding site on anx 2, disrupts the anx 2-S100A10/CFTR complex. Analysis of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and CFTR(inh172)-sensitive currents, taken as indication of the outwardly rectifying Cl(-) channels (ORCC) and CFTR-mediated currents, respectively, showed that Ac1-14, but not N1-14, inhibits both the cAMP/PKA-dependent ORCC and CFTR activities. CaN inhibitors (cypermethrin, cyclosporin A) discriminated between ORCC/CFTR by inhibiting the CFTR(inh172)-, but not the DIDS-sensitive currents, by >70%. Furthermore, peptide Ac1-14 inhibited acetylcholine-induced short-circuit current measured across a sheet of intact intestinal biopsy. Our data suggests that the anx 2-S100A10/CFTR complex is important for CFTR function across epithelia.

Indexed as

Annexin A2CalcineurinCell LineColforsinCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsHumansIn Vitro TechniquesIon Channel GatingProtein BindingS100 Calcium Binding Protein A10S100 ProteinsAnnexin A2CalcineurinColforsinCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorS100 Calcium Binding Protein A10S100 Proteins

Identifiers

PMID17581860
PMCPMC1951747
OpenAlexW2100427094

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.