Evidence map›Paper›PMID 19661060›Full record

ArticleThe Journal of biological chemistry2009

Activation of the TRPV4 ion channel is enhanced by phosphorylation.

Hueng-Chuen Fan, Xuming Zhang, Peter A McNaughton

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

97 citing papers in PubMed, 183 citations in OpenAlex.

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  13. Consideration of Kinase Inhibitors for the Treatment of Hydrocephalus.International journal of molecular sciences · 2023
    Review
  14. Article
  15. Article
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  17. PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022
    Review
  18. Article
  19. Review
  20. Article

37 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 2 countries.

Hueng-Chuen FanDepartment of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom; Department of Pediatrics, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan.
Xuming ZhangDepartment of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom.
Peter A McNaughtonDepartment of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom. Electronic address: pam42@cam.ac.uk.
University of Cambridge · GB

Funding

Biotechnology and Biological Sciences Research Council BB/C003217/1Biotechnology and Biological Sciences Research Council BB/F003072/1
6 · The paper itself

Abstract

The TRPV4 (transient receptor potential vanilloid 4) ion channel, a member of the vanilloid subfamily of the transient receptor potential channels, is activated by membrane stretch, by non-noxious warm temperatures, and by a range of chemical activators. In the present study we examined the role of phosphorylation in modulating the activation of TRPV4. We expressed TRPV4 in HEK293 cells and activated the channel by cell swelling in a hypotonic solution. TRPV4 channel activation and serine phosphorylation were enhanced by exposure to the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate or by application of bradykinin, which activates PKC via a G-protein-coupled mechanism. The enhancement was inhibited by the PKC inhibitors staurosporine, bisindolylmaleimide I, and rottlerin or by mutation of the serine/threonine residues Ser(162), Thr(175), and Ser(189). The adenylate cyclase activator forskolin also enhanced activation of TRPV4, and the enhancement was antagonized by the selective cyclic AMP-dependent protein kinase (PKA) inhibitor H89 or by mutation of serine residue Ser(824). Sensitization of TRPV4 by both PKC and PKA depended on the scaffolding protein AKAP79, because channel activation and phosphorylation were enhanced by co-transfection of AKAP79 and were antagonized by removal of AKAP79 using small interfering RNA. We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.

Indexed as

A Kinase Anchor ProteinsAnimalsBradykininCell LineCyclic AMP-Dependent Protein KinasesEnzyme ActivationEnzyme InhibitorsHumansIon Channel GatingPhorbol EstersPhosphorylationProtein Kinase CRNA, Small InterferingSerineSignal TransductionTRPV Cation ChannelsAKAP5 protein, humanA Kinase Anchor ProteinsBradykininCyclic AMP-Dependent Protein KinasesEnzyme Inhibitorsphorbol-12-myristatePhorbol EstersProtein Kinase CRNA, Small InterferingSerineTRPV4 protein, humanTRPV Cation ChannelsVasodilator Agents

Identifiers

PMID19661060
PMCPMC2788839
OpenAlexW1997882821

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.