Evidence map›Paper›PMID 22851176›Full record

ArticleThe Journal of biological chemistry2012

Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3) coordinates assembly of a multiprotein epithelial sodium channel (ENaC)-regulatory complex.

Rama Soundararajan, Tim Ziera, Eric Koo, Karen Ling, Jian Wang, Steffen A Borden, David Pearce

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Epithelial NaComprehensive Physiology · 2024
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. The Association of a Genetic Variant inJournal of diabetes research · 2017
    Article
  12. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis.International journal of molecular sciences · 2016
    Review
  13. Regulation of the epithelial Na+ channel by the mTORC2/SGK1 pathway.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2016
    Review
  14. Collecting duct principal cell transport processes and their regulation.Clinical journal of the American Society of Nephrology : CJASN · 2015
    Review
  15. Article
  16. Article
  17. 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

7 authors at 2 institutions in 2 countries.

Rama SoundararajanDivision of Nephrology, Department of Medicine, University of California, San Francisco, California 94143, USA.
Tim Ziera
Eric Koo
Karen Ling
Jian Wang
Steffen A Borden
David Pearce
University of California, San Francisco · USBayer (Germany) · DE

Funding

SGK Regulation of Epithelial Sodium TransportR01DK056695 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DAVID PEARCE · 2000 to 2026
$8.1M
GILZ Regulation of ENaCR01DK085101 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PEARCE, DAVID · 2009 to 2012
$1.4M
The Functional Role of GilZ in Epithelial Sodium TransportK01DK078679 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SOUNDARARAJAN, RAMA · 2007 to 2011
$690k
NIDDK NIH HHS K01 DK078679NIDDK NIH HHS K01-DK078679NIDDK NIH HHS R01 DK056695NIDDK NIH HHS R01 DK085101NIDDK NIH HHS R01-DK56695NIDDK NIH HHS R01-DK85101
6 · The paper itself

Abstract

Hormone regulation of ion transport in the kidney tubules is essential for fluid and electrolyte homeostasis in vertebrates. A large body of evidence has suggested that transporters and channels exist in multiprotein regulatory complexes; however, relatively little is known about the composition of these complexes or their assembly. The epithelial sodium channel (ENaC) in particular is tightly regulated by the salt-regulatory hormone aldosterone, which acts at least in part by increasing expression of the serine-threonine kinase SGK1. Here we show that aldosterone induces the formation of a 1.0-1.2-MDa plasma membrane complex, which includes ENaC, SGK1, and the ENaC inhibitor Nedd4-2, a key target of SGK1. We further show that this complex contains the PDZ domain-containing protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3). CNK3 physically interacts with ENaC, Nedd4-2, and SGK1; enhances the interactions among them; and stimulates ENaC function in a PDZ domain-dependent, aldosterone-induced manner. These results strongly suggest that CNK3 is a molecular scaffold, which coordinates the assembly of a multiprotein ENaC-regulatory complex and hence plays a central role in Na(+) homeostasis.

Indexed as

AldosteroneAnimalsEndosomal Sorting Complexes Required for TransportEpithelial Sodium ChannelsHEK293 CellsHomeostasisHumansImmediate-Early ProteinsMembrane ProteinsMiceMultiprotein ComplexesNedd4 Ubiquitin Protein LigasesPDZ DomainsProtein Serine-Threonine KinasesSerum-Glucocorticoid Regulated KinasesSodiumAldosteroneCNKSR3 protein, humanEndosomal Sorting Complexes Required for TransportEpithelial Sodium ChannelsImmediate-Early ProteinsMembrane ProteinsMultiprotein ComplexesNedd4L protein, humanNedd4l protein, mouseNedd4 protein, humanNedd4 Ubiquitin Protein LigasesProtein Serine-Threonine KinasesSerum-Glucocorticoid Regulated KinasesSodiumUbiquitin-Protein Ligases

Identifiers

PMID22851176
PMCPMC3463358
OpenAlexW1988204057

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.