ArticlePflugers Archiv : European journal of physiology2012
Influence of WNK3 on intracellular chloride concentration and volume regulation in HEK293 cells.
Article in Pflugers Archiv : European journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening.Drug design, development and therapy · 2023Article
- Synthesis and Structural Characterization of Novel Trihalo-sulfone Inhibitors of WNK1.ACS medicinal chemistry letters · 2022Article
- Arterial Blood Pressure, Neuronal Excitability, Mineral Metabolism and Cell Volume Regulation Mechanisms Revealed byMembranes · 2022Article
- Molecular mechanisms for the modulation of blood pressure and potassium homeostasis by the distal convoluted tubule.EMBO molecular medicine · 2022Review
- LRRC8A reduces intracellular chloride to permit WNK activation in response to hypertonic stress.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- SIRT7 modulates the stability and activity of the renal K-Cl cotransporter KCC4 through deacetylation.EMBO reports · 2021Article
- Cation-Chloride Cotransporters, Na/K Pump, and Channels in Cell Water and Ion Regulation:Frontiers in cell and developmental biology · 2021Article
- WNK3 and WNK4 exhibit opposite sensitivity with respect to cell volume and intracellular chloride concentration.American journal of physiology. Cell physiology · 2020Article
- Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.Frontiers in physiology · 2020Review
- WNK Kinases in Development and Disease.Current topics in developmental biology · 2017Review
- With no lysine L-WNK1 isoforms are negative regulators of the K+-Cl- cotransporters.American journal of physiology. Cell physiology · 2016Article
- Cellular volume regulation by anoctamin 6: Ca²⁺, phospholipase A2 and osmosensing.Pflugers Archiv : European journal of physiology · 2016Article
- The Effect of WNK4 on the Na+-Cl- Cotransporter Is Modulated by Intracellular Chloride.Journal of the American Society of Nephrology : JASN · 2015Article
- Chloride sensing by WNK1 involves inhibition of autophosphorylation.Science signaling · 2014Article
- The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters.The Biochemical journal · 2014Article
- N-terminal serine dephosphorylation is required for KCC3 cotransporter full activation by cell swelling.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The involvement of WNK3 (with no lysine [K] kinase) in cell volume regulation evoked by anisotonic conditions was investigated in two modified stable lines of HEK293 cells: WNK3+, overexpressing WNK3 and WNK3-KD expressing a kinase inactive by a punctual mutation (D294A) at the catalytic site. This different WNK3 functional expression modified intracellular Cl(-) concentration with the following profile: WNK3+ > control > WNK3-KD cells. Stimulated with 15% hypotonic solutions, WNK3+ cells showed less efficient RVD (13.1%), lower Cl(-) efflux and decreased (94.5%) KCC activity. WNK3-KD cells showed 30.1% more efficient RVD, larger Cl(-) efflux and 5-fold higher KCC activity, increased since the isotonic condition. Volume-sensitive Cl(-) currents were similar in controls, WNK3+ cells, and WNK3-KD cells. Taurine efflux was not evoked at H15%. These results show a WNK3 influence on RVD in HEK293 cells via increasing KCC activity. Hypertonic medium induced cell shrinkage and RVI. In both WNK3+ and WNK3-KD cells, RVI and NKCC activity were increased, in WNK3+ cells presumably by enhanced NKCC phosphorylation, and in WNK3-KD cells via the [Cl(-)](i) reduction induced by the higher KCC activity in characteristic of these cells. These results support the role of WNK3 in modulation of intracellular Cl(-) concentration, in RVD, and indirectly on RVI, via its effects on KCC and NKCC activity. WNK3 in HEK293 cells is expressed as puncta at the intercellular junctions and diffusely at the cytosol, while the inactive kinase was found concentrated at the Golgi area. Cells with inactive WNK3 exhibited a marked change of cell phenotype.
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