ArticleThe Journal of biological chemistry2010
Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- Canagliflozin Inhibits Electrogenic Na+ Transport in Mouse Cortical Collecting Duct Cells.Function (Oxford, England) · 2025Article
- SMURF1/2 Are Novel Regulators of WNK1 Stability.Kinases and phosphatases · 2024Article
- WNK1 is a chloride-stimulated scaffold that regulates mTORC2 activity and ion transport.Journal of cell science · 2022Article
- Kidney ion handling genes and their interaction in blood pressure control.Bioscience reports · 2022Review
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- UBR5 is a novel regulator of WNK1 stability.American journal of physiology. Cell physiology · 2022Article
- WNK1 in Malignant Behaviors: A Potential Target for Cancer?Frontiers in cell and developmental biology · 2022Review
- L-WNK1 is required for BK channel activation in intercalated cells.American journal of physiology. Renal physiology · 2021Article
- The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and pH Homeostasis in Non-Secretory Organs.International journal of molecular sciences · 2020Review
- The Enigmatic Role of Serum & Glucocorticoid Inducible Kinase 1 in the Endometrium.Frontiers in cell and developmental biology · 2020Review
- The signaling role for chloride in the bidirectional communication between neurons and astrocytes.Neuroscience letters · 2019Review
- Review
- Overexpression of WNK1 in POMC-expressing neurons reduces weigh gain via WNK4-mediated degradation of Kir6.2.Molecular and cellular biochemistry · 2018Article
- Increased intracellular ClMucosal immunology · 2018Article
- SGK1 Inhibits Autophagy in Murine Muscle Tissue.Oxidative medicine and cellular longevity · 2018Article
- Akt3 inhibits adipogenesis and protects from diet-induced obesity via WNK1/SGK1 signaling.JCI insight · 2017Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The four WNK (with no lysine (K)) protein kinases affect ion balance and contain an unusual protein kinase domain due to the unique placement of the active site lysine. Mutations in two WNKs cause a heritable form of ion imbalance culminating in hypertension. WNK1 activates the serum- and glucocorticoid-induced protein kinase SGK1; the mechanism is noncatalytic. SGK1 increases membrane expression of the epithelial sodium channel (ENaC) and sodium reabsorption via phosphorylation and sequestering of the E3 ubiquitin ligase neural precursor cell expressed, developmentally down-regulated 4-2 (Nedd4-2), which otherwise promotes ENaC endocytosis. Questions remain about the intrinsic abilities of WNK family members to regulate this pathway. We find that expression of the N termini of all four WNKs results in modest to strong activation of SGK1. In reconstitution experiments in the same cell line all four WNKs also increase sodium current blocked by the ENaC inhibitor amiloride. The N termini of the WNKs also have the capacity to interact with SGK1. More detailed analysis of activation by WNK4 suggests mechanisms in common with WNK1. Further evidence for the importance of WNK1 in this process comes from the ability of Nedd4-2 to bind to WNK1 and the finding that endogenous SGK1 has reduced activity if WNK1 is knocked down by small interfering RNA.
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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.