ArticleHypertension (Dallas, Tex. : 1979)2014
WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4.
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In one paragraph
Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- NRBP1 pseudokinase binds to and activates the WNK pathway in response to osmotic stress.Science advances · 2025Article
- Electrophysiology Models for End-Stage Renal Disease Maladaptations That Promote Asystole.Reviews in cardiovascular medicine · 2025Review
- The evolving concepts of KS-WNK1 effect on NCC activity.American journal of physiology. Renal physiology · 2025Review
- Role of ENaC in gender-associated differences in blood pressure.Iranian journal of basic medical sciences · 2025Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Aldosterone-independent regulation of K + secretion in the distal nephron.Current opinion in nephrology and hypertension · 2024Review
- Deletion of KS-WNK1 promotes NCC activation by increasing WNK1/4 abundance.American journal of physiology. Renal physiology · 2024Article
- Sex differences in dietary sodium evoked NCC regulation and blood pressure in male and female Sprague-Dawley, Dahl salt-resistant, and Dahl salt-sensitive rats.American journal of physiology. Renal physiology · 2024Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023Review
- KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway.BMC nephrology · 2023Article
- SIK3 and Wnk converge on Fray to regulate glial K+ buffering and seizure susceptibility.PLoS genetics · 2023Article
- Blood pressure effects of sodium transport along the distal nephron.Kidney international · 2022Review
- Kidney ion handling genes and their interaction in blood pressure control.Bioscience reports · 2022Review
- Arterial Blood Pressure, Neuronal Excitability, Mineral Metabolism and Cell Volume Regulation Mechanisms Revealed byMembranes · 2022Article
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- Regulation of distal tubule sodium transport: mechanisms and roles in homeostasis and pathophysiology.Pflugers Archiv : European journal of physiology · 2022Review
- Cullin 3 Exon 9 Deletion in Familial Hyperkalemic Hypertension Impairs Cullin3-Ring-E3 Ligase (CRL3) Dynamic Regulation and Cycling.International journal of molecular sciences · 2022Article
- Molecular mechanisms for the modulation of blood pressure and potassium homeostasis by the distal convoluted tubule.EMBO molecular medicine · 2022Review
- NCC regulation by WNK signal cascade.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
María Chávez-CanalesFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Chong ZhangFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Christelle SoukaseumFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Erika MorenoFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Diana Pacheco-AlvarezFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Emmanuelle Vidal-PetiotFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
María Castañeda-BuenoFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Norma VázquezFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Lorena Rojas-VegaFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Nicholas P MeermeierFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Shaunessy RogersFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Xavier JeunemaitreFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Chao-Ling YangFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
David H EllisonFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.).
Gerardo GambaFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.). juliette.hadchouel@inserm.fr gamba@biomedicas.unam.mx.
Juliette HadchouelFrom the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (M.C.-C., E.M., M.C.-B., N.V., L.R.-V., G.G.); Division of Nephrology and Hypertension, Oregon Health and Science University, Portland (C.Z., N.P.M., S.R., X.J., C.-L.Y., D.H.E.); INSERM UMR970-Paris Cardiovascular Research Center, Paris, France (C.S., E.V.-P., X.J., J.H.); Faculty of Medicine, University Paris-Descartes, Sorbonne Paris Cité, Paris, France (C.S., E.V.-P., J.H.); Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico (D.P.-A.); AP-HP, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France (X.J.); and Veterans Affairs Medical Center, Portland, OR (D.H.E.). juliette.hadchouel@inserm.fr gamba@biomedicas.unam.mx.
Universidad Panamericana · MX
Funding
WNK Kinase Regulation of Thiazide-sensitive NaCl TransportR01DK051496 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI David Hoadley Ellison, CHAO-LING YANG · 1998 to 2026
$8.4MRenal Effects of AldosteroneI01BX002228 · VA · PORTLAND VA MEDICAL CENTER · PI ELLISON, DAVID H · 2014 to 2021
–BLRD VA I01 BX002228NIDDK NIH HHS DK51496NIDDK NIH HHS R01 DK051496Wellcome TrustWellcome Trust 091415
Abstract
The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt), associated with an activation of the Na-Cl cotransporter (NCC). Although it is clear that WNK4 mutants activate NCC via Ste20 proline-alanine-rich kinase, the mechanisms responsible for WNK1-related FHHt and alterations in NCC activity are not as clear. We tested whether WNK1 modulates NCC through WNK4, as predicted by some models, by crossing our recently developed WNK1-FHHt mice (WNK1(+/FHHt)) with WNK4(-/-) mice. Surprisingly, the activated NCC, hypertension, and hyperkalemia of WNK1(+/FHHt) mice remain in the absence of WNK4. We demonstrate that WNK1 powerfully stimulates NCC in a WNK4-independent and Ste20 proline-alanine-rich kinase-dependent manner. Moreover, WNK4 decreases the WNK1 and WNK3-mediated activation of NCC. Finally, the formation of oligomers of WNK kinases through their C-terminal coiled-coil domain is essential for their activity toward NCC. In conclusion, WNK kinases form a network in which WNK4 associates with WNK1 and WNK3 to regulate NCC.
Indexed as
AnimalsBlood PressureDisease Models, AnimalFemaleHumansIn Vitro TechniquesKidneyMaleMiceMice, Inbred C57BLMice, KnockoutMice, Mutant StrainsMinor Histocompatibility AntigensPhenotypeProtein Serine-Threonine KinasesPseudohypoaldosteronismMinor Histocompatibility AntigensPrkwnk4 protein, mouseProtein Serine-Threonine KinasesSodium Chloride SymportersStk39 protein, mouseWnk1 protein, mouseWNK Lysine-Deficient Protein Kinase 1familial hypertensive hyperkalemiahypertension, renalkidney tubules, distalmice, knockoutpseudohypoaldosteronism, type IIwater-electrolyte balanceXenopus laevis
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