ArticleProceedings of the National Academy of Sciences of the United States of America2006
WNK1 kinase isoform switch regulates renal potassium excretion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 136 citations in OpenAlex.
- Mechanistic target of rapamycin complex-2 mediates the effect of overnight high KAmerican journal of physiology. Renal physiology · 2026Article
- The Story of Aldosterone Escape.Journal of the American Society of Nephrology : JASN · 2026Review
- Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates.The Journal of clinical investigation · 2025Article
- The evolving concepts of KS-WNK1 effect on NCC activity.American journal of physiology. Renal physiology · 2025Review
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Deletion of KS-WNK1 promotes NCC activation by increasing WNK1/4 abundance.American journal of physiology. Renal physiology · 2024Article
- Monogenic Hypertension Linked to the Renin-Angiotensin-Aldosterone System.Anatolian journal of cardiology · 2024Article
- KS-WNK1 is required for the renal response to extreme changes in potassium intake.American journal of physiology. Renal physiology · 2024Article
- WNK1 is a chloride-stimulated scaffold that regulates mTORC2 activity and ion transport.Journal of cell science · 2022Article
- A narrative review of Hyporeninemic hypertension-an indicator for monogenic forms of hypertension.Pediatric medicine (Hong Kong, China) · 2022Article
- ROMK channels are inhibited in the aldosterone-sensitive distal nephron of renal tubule Nedd4-2-deficient mice.American journal of physiology. Renal physiology · 2022Article
- With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron.Cells · 2021Article
- Non-coding RNAs and the mineralocorticoid receptor in the kidney.Molecular and cellular endocrinology · 2021Review
- Mutation affecting the conserved acidic WNK1 motif causes inherited hyperkalemic hyperchloremic acidosis.The Journal of clinical investigation · 2020Article
- WNK1 regulates uterine homeostasis and its ability to support pregnancy.JCI insight · 2020Article
- The single-cell transcriptomic landscape of early human diabetic nephropathy.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary KAmerican journal of physiology. Renal physiology · 2018Article
- Potassium-regulated distal tubule WNK bodies are kidney-specific WNK1 dependent.Molecular biology of the cell · 2018Article
- A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport.Journal of cellular physiology · 2017Article
- Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC.American journal of physiology. Renal physiology · 2016Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Members of the WNK family of serine/threonine kinases have been implicated as important modulators of salt homeostasis, regulating the balance between renal sodium reabsorption and potassium excretion. Gain-of-expression mutations in the WNK1 gene uncouple Na(+) and K(+) balance and cause a familial disorder of diminished renal potassium excretion, excessive sodium retention, and hypertension (pseudohypoaldosteronism type II or Gordon's syndrome). Alternative splicing of the WNK1 gene produces a kidney-specific short form of WNK1 (KS-WNK1) and a more ubiquitous long form (L-WNK1), but it is not clear how either of these isoforms influence renal potassium excretion. Here we demonstrate that KS-WNK1 and L-WNK1 converge in a pathway to regulate the renal outer-medullary K(+) channel, Kir1.1. Reconstitution studies in Xenopus oocytes reveal that L-WNK1 significantly inhibits Kir1.1 by reducing cell surface localization of the channel. A catalytically inactive L-WNK1 mutant has no inhibitory effect on Kir1.1, indicating that channel inhibition depends on kinase activity. KS-WNK1, lacking an intact kinase domain, does not directly alter Kir1.1. Instead, KS-WNK1 negatively regulates L-WNK1 to release Kir1.1 from inhibition. Acute dietary potassium loading increases the relative abundance of KS-WNK1 to L-WNK1 transcript and protein in the kidney, indicating that physiologic up-regulation of Kir1.1 activity involves a WNK1 isoform switch and KS-WNK1-mediated release from L-WNK1 inhibition. Thus, these observations provide evidence for the physiological regulation of Na(+) and K(+) balance by a kinase isoform switch mechanism.
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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.