ArticleBiology open2012
A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo.
Article in Biology open, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- WNK kinase is a vasoactive chloride sensor in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening.Drug design, development and therapy · 2023Article
- WNK3 inhibition elicits antitumor immunity by suppressing PD-L1 expression on tumor cells and activating T-cell function.Experimental & molecular medicine · 2022Article
- Synthesis and Structural Characterization of Novel Trihalo-sulfone Inhibitors of WNK1.ACS medicinal chemistry letters · 2022Article
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- WNK3 kinase maintains neuronal excitability by reducing inwardly rectifying KFrontiers in molecular neuroscience · 2022Article
- Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.Frontiers in physiology · 2020Review
- The Molecular Genetics of Gordon Syndrome.Genes · 2019Review
- The Drosophila Malpighian tubule as a model for mammalian tubule function.Current opinion in nephrology and hypertension · 2019Review
- Molecular regulation of NKCC2 in blood pressure control and hypertension.Current opinion in nephrology and hypertension · 2019Review
- 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
- The WNK-SPAK/OSR1 Kinases and the Cation-Chloride Cotransporters as Therapeutic Targets for Neurological Diseases.Aging and disease · 2019Review
- WNK4 kinase is a physiological intracellular chloride sensor.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Emerging Targets of Diuretic Therapy.Clinical pharmacology and therapeutics · 2017Review
- WNK signalling pathways in blood pressure regulation.Cellular and molecular life sciences : CMLS · 2017Review
- Article
- Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- WNK Kinases in Development and Disease.Current topics in developmental biology · 2017Review
- Hypertension: the missing WNKs.American journal of physiology. Renal physiology · 2016Review
- A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter.Pflugers Archiv : European journal of physiology · 2015Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII). We previously discovered that WNK kinases phosphorylate and activate OSR1/SPAK kinases that regulate renal SLC12A family transporters such as NKCC2 and NCC, and clarified that the constitutive activation of this cascade causes PHAII. WNK3, another member of the WNK kinase family, was reported to be a strong activator of NCC/NKCC2 when assayed in Xenopus oocytes, suggesting that WNK3 also plays a major role in regulating blood pressure and sodium reabsorption in the kidney. However, it remains to be determined whether WNK3 is in fact involved in the regulation of these transporters in vivo. To clarify this issue, we generated and analyzed WNK3 knockout mice. Surprisingly, phosphorylation and expression of OSR1, SPAK, NKCC2 and NCC did not decrease in knockout mouse kidney under normal and low-salt diets. Similarly, expression of epithelial Na channel and Na/H exchanger 3 were not affected in knockout mice. Na(+) and K(+) excretion in urine in WNK3 knockout mice was not affected under different salt diets. Blood pressure in WNK3 knockout mice was not lower under normal diet. However, lower blood pressure was observed in WNK3 knockout mice fed low-salt diet. WNK4 and WNK1 expression was slightly elevated in the knockout mice under low-salt diet, suggesting compensation for WNK3 knockout by these WNKs. Thus, WNK3 may have some role in the WNK-OSR1/SPAK-NCC/NKCC2 signal cascade in the kidney, but its contribution to total WNK kinase activity may be minimal.
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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.