Evidence map›Paper›PMID 33689398›Full record

ArticleMolecular biology of the cell2021

Osmosensing by WNK Kinases.

Radha Akella, John M Humphreys, Kamil Sekulski, Haixia He, Mateusz Durbacz, Srinivas Chakravarthy, Joanna Liwocha, Zuhair J Mohammed, Chad A Brautigam, Elizabeth J Goldsmith

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. 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
  4. Article
  5. Article
  6. Kinome-wide RNAi screening inJournal of biosciences · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Molecular Crowding: Physiologic Sensing and Control.Annual review of physiology · 2024
    Review
  12. Hydrostatic Pressure Sensing by WNK kinases.Molecular biology of the cell · 2023
    Article
  13. Article
  14. The Integral Role of Chloride & With-No-Lysine Kinases in Cell Volume Regulation & Hypertension.International journal of nephrology and renovascular disease · 2023
    Review
  15. Article
  16. Review
  17. Article
  18. WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  19. Review
  20. LRRC8A reduces intracellular chloride to permit WNK activation in response to hypertonic stress.Proceedings of the National Academy of Sciences of the United States of America · 2021
    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

10 authors at 3 institutions in 1 country.

Radha AkellaDepartment of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
John M HumphreysDepartment of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
Kamil SekulskiDepartment of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
Haixia HeDepartment of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
Mateusz DurbaczDepartment of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
Srinivas ChakravarthyDepartment of Biology, Chemistry, & Physical Sciences, APS/Illinois Institute of Technology, Argonne, IL 60439.
Joanna LiwochaDepartment of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
Zuhair J MohammedBaylor College of Medicine, Houston, TX 77030.
Chad A BrautigamDepartment of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
Elizabeth J GoldsmithDepartment of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
The University of Texas Southwestern Medical Center · USBaylor College of Medicine · USIllinois Institute of Technology · US

Funding

Time resolved SAXS studies on the RP2/Arl3 complex pp.484-485P41GM103622 · NIGMS · ILLINOIS INSTITUTE OF TECHNOLOGY · PI IRVING, THOMAS C · 2012 to 2020
$11.9M
Regulation of WNK signaling by potassium and Mo25: structure, function and physiologyR01DK110358 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI RODAN, AYLIN RACHEL · 2016 to 2025
$4.1M
Advanced Pixel Array Detector for Time-Resolved SAXS and Fiber DiffractionS10OD018090 · OD · ILLINOIS INSTITUTE OF TECHNOLOGY · PI IRVING, THOMAS C · 2014 to 2014
$529k
NIDDK NIH HHS R01 DK110358NIGMS NIH HHS P41 GM103622NIH HHS S10 OD018090
6 · The paper itself

Abstract

With No Lysine (K) WNK kinases regulate electro-neutral cotransporters that are controlled by osmotic stress and chloride. We showed previously that autophosphorylation of WNK1 is inhibited by chloride, raising the possibility that WNKs are activated by osmotic stress. Here we demonstrate that unphosphorylated WNK isoforms 3 and 1 autophosphorylate in response to osmotic pressure in vitro, applied with the crowding agent polyethylene glycol (PEG)400 or osmolyte ethylene glycol (EG), and that this activation is opposed by chloride. Small angle x-ray scattering of WNK3 in the presence and absence of PEG400, static light scattering in EG, and crystallography of WNK1 were used to understand the mechanism. Osmosensing in WNK3 and WNK1 appears to occur through a conformational equilibrium between an inactive, unphosphorylated, chloride-binding dimer and an autophosphorylation-competent monomer. An improved structure of the inactive kinase domain of WNK1, and a comparison with the structure of a monophosphorylated form of WNK1, suggests that large cavities, greater hydration, and specific bound water may participate in the osmosensing mechanism. Our prior work showed that osmolytes have effects on the structure of phosphorylated WNK1, suggestive of multiple stages of osmotic regulation in WNKs.

Indexed as

AutoradiographyChromatography, GelEthylene GlycolOsmotic PressurePhosphorylationPolyethylene GlycolsProtein ConformationProtein KinasesProtein MultimerizationScattering, Small AngleWaterWNK Lysine-Deficient Protein Kinase 1X-Ray DiffractionEthylene Glycolpolyethylene glycol 400Polyethylene GlycolsProtein KinasesWaterWnk1 protein, ratWnk3 protein, ratWNK Lysine-Deficient Protein Kinase 1

Identifiers

PMID33689398
PMCPMC8684725
OpenAlexW3135476645

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
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 Socratic graph.