ArticleJournal of the American Society of Nephrology : JASN2013
SPAK differentially mediates vasopressin effects on sodium cotransporters.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 96 citations in OpenAlex.
- Neuraminidase1 Activity Contributes to Vasopressin Receptor-mediated Augmentation of Water and Electrolyte Retention by the Kidney inbioRxiv : the preprint server for biology · 2026Article
- Molecular Basis of Rare Inherited Tubulopathies of the Kidney: A Primer for Clinicians.International journal of molecular sciences · 2026Review
- Calcium-binding protein 39 in with-no-lysine kinase signaling and the modulation of renal tubular transport.Current opinion in nephrology and hypertension · 2025Review
- Disruption of mitochondrial electron transport impairs urinary concentration via AMPK-dependent suppression of aquaporin 2.JCI insight · 2024Article
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Kidney collecting duct-derived vasopressin is not essential for appropriate concentration or dilution of urine.American journal of physiology. Renal physiology · 2024Article
- Arginine vasopressin regulates the renal NaAmerican journal of physiology. Renal physiology · 2024Article
- Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions.Frontiers in physiology · 2024Review
- Dysregulation of the WNK4-SPAK/OSR1 pathway has a minor effect on baseline NKCC2 phosphorylation.American journal of physiology. Renal physiology · 2024Article
- Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023Review
- The serine-threonine protein phosphatases that regulate the thiazide-sensitive NaCl cotransporter.Frontiers in physiology · 2023Review
- Chronic activation of vasopressin-2 receptors induces hypertension in Liddle mice by promoting NaAmerican journal of physiology. Renal physiology · 2022Article
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- A five amino acids deletion in NKCC2 of C57BL/6 mice affects analysis of NKCC2 phosphorylation but does not impact kidney function.Acta physiologica (Oxford, England) · 2021Article
- Activation of the Thiazide-Sensitive Sodium-Chloride Cotransporter by Beta3-Adrenoreceptor in the Distal Convoluted Tubule.Frontiers in physiology · 2021Article
- Review
- PKA-independent vasopressin signaling in renal collecting duct.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Identification and characterization of alternative STK39 transcripts within human and mouse kidneys reveals species-specific regulation of blood pressure.Physiological reports · 2020Article
- The interplay of renal potassium and sodium handling in blood pressure regulation: critical role of the WNK-SPAK-NCC pathway.Journal of human hypertension · 2019Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
Activation of the Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) and the Na(+)-Cl(-)-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine and serine residues, but the kinase pathways that mediate this action of vasopressin are not well understood. Two homologous Ste20-like kinases, SPS-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive kinase (OSR1), can phosphorylate the cotransporters directly. In this process, a full-length SPAK variant and OSR1 interact with a truncated SPAK variant, which has inhibitory effects. Here, we tested whether SPAK is an essential component of the vasopressin stimulatory pathway. We administered desmopressin, a V2 receptor-specific agonist, to wild-type mice, SPAK-deficient mice, and vasopressin-deficient rats. Desmopressin induced regulatory changes in SPAK variants, but not in OSR1 to the same degree, and activated NKCC2 and NCC. Furthermore, desmopressin modulated both the full-length and truncated SPAK variants to interact with and phosphorylate NKCC2, whereas only full-length SPAK promoted the activation of NCC. In summary, these results suggest that SPAK mediates the effect of vasopressin on sodium reabsorption along the distal nephron.
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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.