ArticleAmerican journal of physiology. Renal physiology2011
WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK.American journal of physiology. Renal physiology · 2025Article
- Circadian Rhythm Regulation by Pacemaker Neuron Chloride Oscillation in Flies.Physiology (Bethesda, Md.) · 2024Review
- Chloride oscillation in pacemaker neurons regulates circadian rhythms through a chloride-sensing WNK kinase signaling cascade.Current biology : CB · 2022Article
- 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
- MST3 Involvement in NaInternational journal of molecular sciences · 2021Article
- 14-3-3γ, a novel regulator of the large-conductance CaAmerican journal of physiology. Renal physiology · 2020Article
- Stimulatory Role of SPAK Signaling in the Regulation of Large Conductance CaFrontiers in physiology · 2020Article
- The Molecular Genetics of Gordon Syndrome.Genes · 2019Review
- Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology.Seminars in nephrology · 2019Review
- Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels.Frontiers in physiology · 2017Review
- Alcohol Regulates BK Surface Expression via Wnt/β-Catenin Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron.American journal of physiology. Cell physiology · 2016Review
- Cell-specific regulation of L-WNK1 by dietary K.American journal of physiology. Renal physiology · 2016Article
- Regulatory Crosstalk by Protein Kinases on CFTR Trafficking and Activity.Frontiers in chemistry · 2016Review
- WNK1 activates large-conductance Ca2+-activated K+ channels through modulation of ERK1/2 signaling.Journal of the American Society of Nephrology : JASN · 2015Article
- Dietary potassium and the renal control of salt balance and blood pressure.Pflugers Archiv : European journal of physiology · 2015Review
- Collecting duct intercalated cell function and regulation.Clinical journal of the American Society of Nephrology : CJASN · 2015Review
- Article
- Interacting influence of diuretics and diet on BK channel-regulated K homeostasis.Current opinion in pharmacology · 2014Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
WNK [with no lysine (k)] kinase is a serine/threonine kinase subfamily. Mutations in two of the WNK kinases result in pseudohypoaldosteronism type II (PHA II) characterized by hypertension, hyperkalemia, and metabolic acidosis. Recent studies showed that both WNK1 and WNK4 inhibit ROMK activity. However, little is known about the effect of WNK kinases on Maxi K, a large-conductance Ca(2+) and voltage-activated potassium (K) channel. Here, we report that WNK4 wild-type (WT) significantly inhibits Maxi K channel activity in HEK αBK stable cell lines compared with the control group. However, a WNK4 dead-kinase mutant, D321A, has no inhibitory effect on Maxi K activity. We further found that WNK4 inhibits total and cell surface protein expression of Maxi K equally compared with control groups. A dominant-negative dynamin mutant, K44A, did not alter the WNK4-mediated inhibitory effect on Maxi K surface expression. Treatment with bafilomycin A1 (a proton pump inhibitor) and leupeptin (a lysosomal inhibitor) reversed WNK4 WT-mediated inhibition of Maxi K total protein expression. These findings suggest that WNK4 WT inhibits Maxi K activity by reducing Maxi K protein at the membrane, but that the inhibition is not due to an increase in clathrin-mediated endocytosis of Maxi K, but likely due to enhancing its lysosomal degradation. Also, WNK4's inhibitory effect on Maxi K activity is dependent on its kinase activity.
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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.