Evidence map›Paper›PMID 36373794›Full record

ArticleJournal of cell science2022

WNK1 is a chloride-stimulated scaffold that regulates mTORC2 activity and ion transport.

Bidisha Saha, Deise C A Leite-Dellova, John Demko, Mads Vaarby Sørensen, Enzo Takagi, Catherine E Gleason, Waheed Shabbir, David Pearce

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-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

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Central Osmolality Sensing for Arginine Vasopressin Release Is Mediated by WNK1-OSR1/SPAK-Kv3.1 Cascade.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024
    Review
  7. Review
  8. Aldosterone-independent regulation of K + secretion in the distal nephron.Current opinion in nephrology and hypertension · 2024
    Review
  9. Review
  10. Article
  11. Constituents ofMolecules (Basel, Switzerland) · 2024
    Article
  12. Anoctamin-1 is induced by TGF-β and contributes to lung myofibroblast differentiation.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  13. Physiological roles of chloride ions in bodily and cellular functions.The journal of physiological sciences : JPS · 2023
    Review
  14. Article
  15. Consideration of Kinase Inhibitors for the Treatment of Hydrocephalus.International journal of molecular sciences · 2023
    Review
  16. 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

8 authors at 3 institutions in 3 countries.

Bidisha SahaDivision of Nephrology, Departments of Medicine and Cellular & Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
Deise C A Leite-DellovaDepartment of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Sao Paulo 13635-900, Brazil.
John DemkoDivision of Nephrology, Departments of Medicine and Cellular & Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
Mads Vaarby SørensenDepartments of Biomedicine and Physiology, Aarhus University, 8000 Aarhus C, Denmark.
Enzo TakagiDivision of Nephrology, Departments of Medicine and Cellular & Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
Catherine E GleasonDivision of Nephrology, Departments of Medicine and Cellular & Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
Waheed ShabbirDivision of Nephrology, Departments of Medicine and Cellular & Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
David PearceDivision of Nephrology, Departments of Medicine and Cellular & Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0003-0496-3173
University of California, San Francisco · USAarhus University · DKUniversidade de São Paulo · BR

Funding

SGK Regulation of Epithelial Sodium TransportR01DK056695 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DAVID PEARCE · 2000 to 2026
$8.1M
Academic Training Program in NephrologyT32DK007219 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HSU, CHI-YUAN · 1986 to 2022
$7.3M
NIDDK NIH HHS R01 DK056695NIDDK NIH HHS T32 DK007219NIH HHS R01-DK56695
6 · The paper itself

Abstract

Mammalian (or mechanistic) target of rapamycin complex 2 (mTORC2) is a kinase complex that targets predominantly Akt family proteins, SGK1 and protein kinase C (PKC), and has well-characterized roles in mediating hormone and growth factor effects on a wide array of cellular processes. Recent evidence suggests that mTORC2 is also directly stimulated in renal tubule cells by increased extracellular K+ concentration, leading to activation of the Na+ channel, ENaC, and increasing the electrical driving force for K+ secretion. We identify here a signaling mechanism for this local effect of K+. We show that an increase in extracellular [K+] leads to a rise in intracellular chloride (Cl-), which stimulates a previously unknown scaffolding activity of the protein 'with no lysine-1' (WNK1) kinase. WNK1 interacts selectively with SGK1 and recruits it to mTORC2, resulting in enhanced SGK1 phosphorylation and SGK1-dependent activation of ENaC. This scaffolding effect of WNK1 is independent of its own kinase activity and does not cause a generalized stimulation of mTORC2 kinase activity. These findings establish a novel WNK1-dependent regulatory mechanism that harnesses mTORC2 kinase activity selectively toward SGK1 to control epithelial ion transport and electrolyte homeostasis.

Indexed as

Immediate-Early ProteinsAnimalsChloridesEpithelial Sodium ChannelsIon TransportMammalsMechanistic Target of Rapamycin Complex 2Minor Histocompatibility AntigensProtein Serine-Threonine KinasesTOR Serine-Threonine KinasesChloridesEpithelial Sodium ChannelsImmediate-Early ProteinsMechanistic Target of Rapamycin Complex 2Minor Histocompatibility AntigensProtein Serine-Threonine KinasesTOR Serine-Threonine KinasesElectrolytesENaCIon transportK+ homeostasisKidney epithelial cellsmTORmTORC2Protein–protein interactionRictorSGK1WNK1WNK kinase

Identifiers

PMID36373794
PMCPMC9789407
OpenAlexW4308957437

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.