ArticleCell metabolism2011
A SPAK isoform switch modulates renal salt transport and blood pressure.
Article in Cell metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed, 206 citations in OpenAlex.
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- STK39 promotes the evolution cascade of hepatocellular carcinoma by facilitating PKR/NF-κB-mediated macrophage inflammatory response.Oncogene · 2026Article
- Kidney kallikrein-1 contributes to cleavage of γ-ENaC in vivo.American journal of physiology. Renal physiology · 2026Article
- Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK.The Journal of physiology · 2025Article
- Mechanistic Target of Rapamycin Complex 1 in Distal Convoluted Tubule and Renal Potassium Handling.Journal of the American Society of Nephrology : JASN · 2025Article
- Kidney kallikrein-1 contributes to cleavage of gamma-ENaCbioRxiv : the preprint server for biology · 2025Article
- Calcium-binding protein 39 in with-no-lysine kinase signaling and the modulation of renal tubular transport.Current opinion in nephrology and hypertension · 2025Review
- Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates.The Journal of clinical investigation · 2025Article
- Hypomagnesemia: exploring its multifaceted health impacts and associations with blood pressure regulation and metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- A salty symphony: unraveling the tale of uromodulin and sodium sensitivity.Journal of human hypertension · 2025Review
- STK39 inhibits antiviral immune response by inhibiting DCAF1-mediated PP2A degradation.Acta pharmaceutica Sinica. B · 2025Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- STK39-mediated amplification of γ-H2A.X promotes homologous recombination and contributes to PARP inhibitor resistance.Nucleic acids research · 2024Article
- Integrated renal and sympathetic mechanisms underlying the development of sex- and age-dependent hypertension and the salt sensitivity of blood pressure.GeroScience · 2024Article
- Macrophage SPAK deletion limits a low potassium-induced kidney inflammatory program.American journal of physiology. Renal physiology · 2024Article
- A New Phase for WNK Kinase Signaling Complexes as Biomolecular Condensates.Physiology (Bethesda, Md.) · 2024Review
- Deletion of KS-WNK1 promotes NCC activation by increasing WNK1/4 abundance.American journal of physiology. Renal physiology · 2024Article
- Role of calcineurin in regulating renal potassium (KActa physiologica (Oxford, England) · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2.Nature communications · 2024Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The renal thick ascending limb (TAL) and distal convoluted tubule (DCT) play central roles in salt homeostasis and blood pressure regulation. An emerging model suggests that bumetanide- and thiazide-sensitive NaCl transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1. Here, we show that a kidney-specific SPAK isoform, which lacks the kinase domain, inhibits phosphorylation of NCC and NKCC2 by full-length SPAK in vitro. Kidney-specific SPAK is highly expressed along the TAL, whereas full-length SPAK is more highly expressed along the DCT. As predicted from the differential expression, SPAK knockout in animals has divergent effects along TAL and DCT, with increased phosphorylated NKCC2 along TAL and decreased phosphorylated NCC along DCT. In mice, extracellular fluid volume depletion shifts SPAK isoform abundance to favor NaCl retention along both segments, indicating that a SPAK isoform switch modulates sodium avidity along the distal nephron.
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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.