Evidence map›Paper›PMID 25362046›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK.

Hashem A Dbouk, Lauren M Weil, G K Sachith Perera, Michael T Dellinger, Gray Pearson, Rolf A Brekken, Melanie H Cobb

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

45 citing papers in PubMed, 73 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Activation of WNK1 signaling through Piezo1.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. CFTR as a therapeutic target for severe lung infection.American journal of physiology. Lung cellular and molecular physiology · 2025
    Review
  9. Article
  10. Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. WNK kinase is a vasoactive chloride sensor in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. WNK1 controls endosomal trafficking through TRIM27-dependent regulation of actin assembly.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Article
  18. Article
  19. Review
  20. 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
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 1 country.

Hashem A DboukDepartments of Pharmacology and.
Lauren M WeilDepartments of Pharmacology and.
G K Sachith PereraDepartments of Pharmacology and.
Michael T DellingerSurgery.
Gray PearsonDepartments of Pharmacology and Simmons Comprehensive Cancer Center, and.
Rolf A BrekkenDepartments of Pharmacology and Surgery, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Melanie H CobbDepartments of Pharmacology and melanie.cobb@utsouthwestern.edu.
The University of Texas at Austin · USSouthwestern Medical Center · US

Funding

REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASESR01GM053032 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI COBB, MELANIE H. · 1995 to 2012
$4.6M
Investigating Breast Cancer Collective InvasionR01CA155241 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI PEARSON, GRAY W · 2011 to 2015
$1.6M
Matricellular proteins as regulators of tumor progressionR01CA118240 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI BREKKEN, ROLF A · 2007 to 2010
$1.2M
NCI NIH HHS R01 CA115241NCI NIH HHS R01 CA118240NCI NIH HHS R01 CA155241NIGMS NIH HHS R01 GM053032NIGMS NIH HHS R01 GM53032
6 · The paper itself

Abstract

The with no lysine (K) (WNK) family of enzymes is best known for control of blood pressure through regulation of the function and membrane localization of ion cotransporters. In mice, global as well as endothelial-specific WNK1 gene disruption results in embryonic lethality due to angiogenic and cardiovascular defects. WNK1(-/-) embryos can be rescued by endothelial-specific expression of a constitutively active form of the WNK1 substrate protein kinase OSR1 (oxidative stress responsive 1). Using human umbilical vein endothelial cells (HUVECs), we explored mechanisms underlying the requirement of WNK1-OSR1 signaling for vascular development. WNK1 is required for cord formation in HUVECs, but the actions of the two major WNK1 effectors, OSR1 and its close relative SPAK (STE20/SPS1-related proline-, alanine-rich kinase), are distinct. SPAK is important for endothelial cell proliferation, whereas OSR1 is required for HUVEC chemotaxis and invasion. We also identified the zinc-finger transcription factor Slug in WNK1-mediated control of endothelial functions. Our study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells and an unanticipated link between WNK1 and Slug that is important for angiogenesis.

Indexed as

AnimalsCell ProliferationGene Expression RegulationHumansHuman Umbilical Vein Endothelial CellsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMinor Histocompatibility AntigensNeovascularization, PhysiologicProtein Serine-Threonine KinasesSignal TransductionSnail Family Transcription FactorsTranscription FactorsWNK Lysine-Deficient Protein Kinase 1Intracellular Signaling Peptides and ProteinsMinor Histocompatibility AntigensOXSR1 protein, humanOXSR1 protein, mouseProtein Serine-Threonine KinasesSNAI1 protein, humanSnai2 protein, mouseSnail Family Transcription FactorsSTK39 protein, humanStk39 protein, mouseTranscription FactorsWNK1 protein, humanWnk1 protein, mouseWNK Lysine-Deficient Protein Kinase 1angiogenesisEMTendotheliummigrationSlug

Identifiers

PMID25362046
PMCPMC4234555
OpenAlexW2090456972

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.