ArticleAmerican journal of physiology. Renal physiology2008
WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway.
Article in American journal of physiology. Renal physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Single nucleus RNA sequencing identifies PLXNA4 upregulation in end-stage arrhythmogenic right ventricular cardiomyopathy.iScience · 2026Article
- PHPT1 acts as an inhibitor in high-altitude pulmonary hypertension via negative TRPV5 signaling regulation.Journal of translational medicine · 2025Article
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- Calcium selective channel TRPV6: Structure, function, and implications in health and disease.Gene · 2022Review
- CCT and CCT-Like Modular Protein Interaction Domains in WNK Signaling.Molecular pharmacology · 2022Review
- Article
- Hypertension: the missing WNKs.American journal of physiology. Renal physiology · 2016Review
- First evidence of TRPV5 and TRPV6 channels in human parathyroid glands: possible involvement in neoplastic transformation.Journal of cellular and molecular medicine · 2014Article
- Regulation of the epithelial Ca²⁺ channel TRPV5 by reversible histidine phosphorylation mediated by NDPK-B and PHPT1.Molecular biology of the cell · 2014Article
- Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- LINGO-1 receptor promotes neuronal apoptosis by inhibiting WNK3 kinase activity.The Journal of biological chemistry · 2013Article
- Disease-causing R1185C mutation of WNK4 disrupts a regulatory mechanism involving calmodulin binding and SGK1 phosphorylation sites.American journal of physiology. Renal physiology · 2013Article
- WNK kinases and the kidney.Experimental cell research · 2012Review
- Disease-causing mutations in the acidic motif of WNK4 impair the sensitivity of WNK4 kinase to calcium ions.Biochemical and biophysical research communications · 2012Article
- Variations of dietary salt and fluid modulate calcium and magnesium transport in the renal distal tubule.Nephron. Physiology · 2012Article
- The WNKs: atypical protein kinases with pleiotropic actions.Physiological reviews · 2011Review
- Down-regulation of intestinal apical calcium entry channel TRPV6 by ubiquitin E3 ligase Nedd4-2.The Journal of biological chemistry · 2010Article
- Pathophysiological roles of WNK kinases in the kidney.Pflugers Archiv : European journal of physiology · 2010Review
- Emerging roles for WNK kinases in cancer.Cellular and molecular life sciences : CMLS · 2010Review
- The A563T variation of the renal epithelial calcium channel TRPV5 among African Americans enhances calcium influx.American journal of physiology. Renal physiology · 2009Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
WNK3, a member of the With No Lysine (K) family of protein serine/threonine kinases, was shown to regulate members of the SLC12A family of cation-chloride cotransporters and the renal outer medullary K+ channel ROMK and Cl(-) channel SLC26A9. To evaluate the effect of WNK3 on TRPV5, a renal epithelial Ca2+ channel that serves as a gatekeeper for active Ca2+ reabsorption, WNK3 and TRPV5 were coexpressed in Xenopus laevis oocytes and the function and expression of TRPV5 were subsequently examined. An 82.7 +/- 7.1% increase in TRPV5-mediated Ca2+ uptake was observed when WNK3 was coexpressed. A similar increase in TRPV5-mediated Na+ current was observed with the voltage-clamp technique. WNK3 also enhanced Ca2+ influx and Na+ current mediated by TRPV6, which is the closest homolog of TRPV5 that mediates active intestinal Ca2+ absorption. The kinase domain of WNK3 alone was sufficient to increase TRPV5-mediated Ca2+ transport, and the positive regulatory effect was abolished by the kinase-inactive D294A mutation in WNK3, indicating a kinase-dependent mechanism. The complexly glycosylated TRPV5 that appears at the plasma membrane was increased by WNK3. The exocytosis of TRPV5 was increased by WNK3, and the effect of WNK3 on TRPV5 was abolished by the microtubule inhibitor colchicine. The increased plasma membrane expression of TRPV5 was likely due to the enhanced delivery of mature TRPV5 to the plasma membrane from its intracellular pool via the secretory pathway. These results indicate that WNK3 is a positive regulator of the transcellular Ca2+ transport pathway.
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