ArticleAmerican journal of physiology. Renal physiology2013
WNK4 inhibition of ENaC is independent of Nedd4-2-mediated ENaC ubiquitination.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Risk factors for renal impairment in primary aldosteronism: a retrospective study.Frontiers in endocrinology · 2025Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Distal convoluted tubule-specific disruption of the COP9 signalosome but not its regulatory target cullin 3 causes tubular injury.American journal of physiology. Renal physiology · 2024Article
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- Aldosterone-Regulated Sodium Transport and Blood Pressure.Frontiers in physiology · 2022Review
- L-WNK1 is required for BK channel activation in intercalated cells.American journal of physiology. Renal physiology · 2021Article
- WNK4 kinase: from structure to physiology.American journal of physiology. Renal physiology · 2021Review
- Mechanisms coupling sodium and magnesium reabsorption in the distal convoluted tubule of the kidney.Acta physiologica (Oxford, England) · 2021Review
- Article
- Loss of primary cilia increases polycystin-2 and TRPV4 and the appearance of a nonselective cation channel in the mouse cortical collecting duct.American journal of physiology. Renal physiology · 2019Article
- Upregulation of the WNK4 Signaling Pathway Inhibits Epithelial Sodium Channels of Mouse Tracheal Epithelial Cells After Influenza A Infection.Frontiers in pharmacology · 2019Article
- Aldosterone, SGK1, and ion channels in the kidney.Clinical science (London, England : 1979) · 2018Review
- Regulation of Transporters and Channels by Membrane-Trafficking Complexes in Epithelial Cells.Cold Spring Harbor perspectives in biology · 2017Review
- Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport.Expert opinion on therapeutic targets · 2017Review
- Alveolar nonselective channels are ASIC1a/α-ENaC channels and contribute to AFC.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- WNK signalling pathways in blood pressure regulation.Cellular and molecular life sciences : CMLS · 2017Review
- ENaC and ROMK activity are inhibited in the DCT2/CNT of TgWnk4American journal of physiology. Renal physiology · 2017Article
- Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7).The Journal of biological chemistry · 2016Article
- Regulatory Crosstalk by Protein Kinases on CFTR Trafficking and Activity.Frontiers in chemistry · 2016Review
- Calmodulin and CaMKII modulate ENaC activity by regulating the association of MARCKS and the cytoskeleton with the apical membrane.American journal of physiology. Renal physiology · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
A serine-threonine protein kinase, WNK4, reduces Na⁺ reabsorption and K⁺ secretion in the distal convoluted tubule by reducing trafficking of the thiazide-sensitive Na-Cl cotransporter to and enhancing renal outer medullary potassium channel retrieval from the apical membrane. Epithelial sodium channels (ENaC) in the distal nephron also play a role in regulating Na⁺ reabsorption and are also regulated by WNK4, but the mechanism is unclear. In A6 distal nephron cells, transepithelial current measurement and single channel recording show that WNK4 inhibits ENaC activity. Analysis of the number of channel per patch shows that WNK4 reduces channel number but has no effect on channel open probability. Western blots of apical and total ENaC provide additional evidence that WNK4 reduces apical as well as total ENaC expression. WNK4 enhances ENaC internalization independent of Nedd4-2-mediated ENaC ubiquitination. WNK4 also reduced the amount of ENaC available for recycling but has no effect on the rate of transepithelial current increase to forskolin. In contrast, Nedd4-2 not only reduced ENaC in the recycling pool but also decreased the rate of increase of current after forskolin. WNK4 associates with wild-type as well as Liddle's mutated ENaC, and WNK4 reduces both wild-type and mutated ENaC expressed in HEK293 cells.
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Registered trials
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.