Evidence map›Paper›PMID 20817728›Full record

ArticleThe Journal of biological chemistry2010

Allosteric inhibition of the epithelial Na+ channel through peptide binding at peripheral finger and thumb domains.

Ossama B Kashlan, Cary R Boyd, Christos Argyropoulos, Sora Okumura, Rebecca P Hughey, Michael Grabe, Thomas R Kleyman

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
–field-weighted citation impact
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

39 citing papers in PubMed.

  1. Article
  2. Epithelial Na+ Channels, Immune Cells, and Salt.Annual review of physiology · 2025
    Review
  3. Article
  4. Epithelial NaComprehensive Physiology · 2024
    Review
  5. Elevated intracellular NaProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  6. Article
  7. Article
  8. Regulating ENaC's gate.American journal of physiology. Cell physiology · 2020
    Review
  9. Murine epithelial sodium (NaThe Journal of biological chemistry · 2019
    Article
  10. Review
  11. Thumb domains of the three epithelial NaThe Journal of biological chemistry · 2018
    Article
  12. The epithelial NaThe Journal of biological chemistry · 2018
    Article
  13. Article
  14. Conserved cysteines in the finger domain of the epithelial NaThe Journal of biological chemistry · 2018
    Article
  15. Article
  16. Epithelial NaAnnual review of physiology · 2018
    Review
  17. Article
  18. Review
  19. Review
  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

7 authors.

Ossama B KashlanDepartments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Cary R Boyd
Christos Argyropoulos
Sora Okumura
Rebecca P Hughey
Michael Grabe
Thomas R Kleyman

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Biomechanical Regulation of Renal Ion TransportersR37DK051391 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2006 to 2015
$3.2M
Sodium Channel BiogenesisR01DK065161 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUGHEY, REBECCA P, KLEYMAN, THOMAS R · 2004 to 2013
$2.8M
SODIUM CHANNELS IN THE MAMMALIAN URINARY BLADDERR01DK051391 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R. · 1996 to 2005
$1.5M
Organization and Structure of ENaC Transmembrane SegmentsK01DK078734 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KASHLAN, OSSAMA B · 2008 to 2012
$706k
Sodium Channel BiogenesisR56DK065161 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUGHEY, REBECCA P, KLEYMAN, THOMAS R · 2008 to 2008
$226k
NIDDK NIH HHS DK051391NIDDK NIH HHS DK065161NIDDK NIH HHS DK078734NIDDK NIH HHS DK079307NIDDK NIH HHS K01 DK078734NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK051391NIDDK NIH HHS R01 DK065161NIDDK NIH HHS R37 DK051391NIDDK NIH HHS R56 DK065161
6 · The paper itself

Abstract

The epithelial Na(+) channel (ENaC) mediates the rate-limiting step in transepithelial Na(+) transport in the distal segments of the nephron and in the lung. ENaC subunits are cleaved by proteases, resulting in channel activation due to the release of inhibitory tracts. Peptides derived from these tracts inhibit channel activity. The mechanism by which these intrinsic inhibitory tracts reduce channel activity is unknown, as are the sites where these tracts interact with other residues within the channel. We performed site-directed mutagenesis in large portions of the predicted periphery of the extracellular region of the α subunit and measured the effect of mutations on an 8-residue inhibitory tract-derived peptide. Our data show that the inhibitory peptide likely binds to specific residues within the finger and thumb domains of ENaC. Pairwise interactions between the peptide and the channel were identified by double mutant cycle experiments. Our data suggest that the inhibitory peptide has a specific peptide orientation within its binding site. Extended to the intrinsic inhibitory tract, our data suggest that proteases activate ENaC by removing residues that bind at the finger-thumb domain interface.

Indexed as

Epithelial Sodium Channel BlockersAllosteric RegulationAnimalsBinding SitesEpithelial Sodium ChannelsMiceMutationPeptidesProtein Structure, TertiaryProtein SubunitsXenopus laevisEpithelial Sodium Channel BlockersEpithelial Sodium ChannelsPeptidesProtein Subunits

Identifiers

PMID20817728
PMCPMC2966135

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.