ArticleJournal of the American Society of Nephrology : JASN2015
WNK1 activates large-conductance Ca2+-activated K+ channels through modulation of ERK1/2 signaling.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Activation of BK channels ameliorates cardiac injury Via NFκB-NLRP3 signaling in angiotensin II-induced hypertension mouse model.Frontiers in pharmacology · 2026Article
- The exquisite link between potassium homeostasis regulation and cardiovascular health: exploration and analysis.Frontiers in physiology · 2026Review
- Activation of BK channels prevents diabetes-induced osteopenia by regulating mitochondrial CaAutophagy · 2024Article
- Circadian Rhythm Regulation by Pacemaker Neuron Chloride Oscillation in Flies.Physiology (Bethesda, Md.) · 2024Review
- Editorial: New advances in the renal regulation of KFrontiers in physiology · 2023Article
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- Chloride oscillation in pacemaker neurons regulates circadian rhythms through a chloride-sensing WNK kinase signaling cascade.Current biology : CB · 2022Article
- WNK3 kinase maintains neuronal excitability by reducing inwardly rectifying KFrontiers in molecular neuroscience · 2022Article
- WNK1 in Malignant Behaviors: A Potential Target for Cancer?Frontiers in cell and developmental biology · 2022Review
- L-WNK1 is required for BK channel activation in intercalated cells.American journal of physiology. Renal physiology · 2021Article
- With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron.Cells · 2021Article
- BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke.Frontiers in cellular neuroscience · 2021Article
- 14-3-3γ, a novel regulator of the large-conductance CaAmerican journal of physiology. Renal physiology · 2020Article
- Intercalated cell BKα subunit is required for flow-induced K+ secretion.JCI insight · 2020Article
- Stimulatory Role of SPAK Signaling in the Regulation of Large Conductance CaFrontiers in physiology · 2020Article
- The Molecular Genetics of Gordon Syndrome.Genes · 2019Review
- Sex-Dependent Signaling Pathways Underlying Seizure Susceptibility and the Role of Chloride Cotransporters.Cells · 2019Review
- The renal response to potassium stress: integrating past with present.Current opinion in nephrology and hypertension · 2017Review
- Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium Depletion.Journal of the American Society of Nephrology : JASN · 2017Article
- Double Knockout of the Na+-Driven Cl-/HCO3- Exchanger and Na+/Cl- Cotransporter Induces Hypokalemia and Volume Depletion.Journal of the American Society of Nephrology : JASN · 2017Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
With no lysine (WNK) kinases are members of the serine/threonine kinase family. We previously showed that WNK4 inhibits renal large-conductance Ca(2+)-activated K(+) (BK) channel activity by enhancing its degradation through a lysosomal pathway. In this study, we investigated the effect of WNK1 on BK channel activity. In HEK293 cells stably expressing the α subunit of BK (HEK-BKα cells), siRNA-mediated knockdown of WNK1 expression significantly inhibited both BKα channel activity and open probability. Knockdown of WNK1 expression also significantly inhibited BKα protein expression and increased ERK1/2 phosphorylation, whereas overexpression of WNK1 significantly enhanced BKα expression and decreased ERK1/2 phosphorylation in a dose-dependent manner in HEK293 cells. Knockdown of ERK1/2 prevented WNK1 siRNA-mediated inhibition of BKα expression. Similarly, pretreatment of HEK-BKα cells with the lysosomal inhibitor bafilomycin A1 reversed the inhibitory effects of WNK1 siRNA on BKα expression in a dose-dependent manner. Knockdown of WNK1 expression also increased the ubiquitination of BKα channels. Notably, mice fed a high-K(+) diet for 10 days had significantly higher renal protein expression levels of BKα and WNK1 and lower levels of ERK1/2 phosphorylation compared with mice fed a normal-K(+) diet. These data suggest that WNK1 enhances BK channel function by reducing ERK1/2 signaling-mediated lysosomal degradation of the channel.
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