ArticleProceedings of the National Academy of Sciences of the United States of America2019
Calcineurin dephosphorylates Kelch-like 3, reversing phosphorylation by angiotensin II and regulating renal electrolyte handling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.The Journal of clinical investigation · 2025Trial
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Piezo1 dictates KProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Activation of WNK1 signaling through Piezo1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- GADD45α is a direct target of TFEB and contributes to tacrolimus-induced chronic nephrotoxicity.JCI insight · 2025Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Disorders of potassium homeostasis after kidney transplantation.World journal of transplantation · 2024Review
- Role of calcineurin in regulating renal potassium (KActa physiologica (Oxford, England) · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Potassium-Switch Signaling Pathway Dictates Acute Blood Pressure Response to Dietary Potassium.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure.The Journal of clinical investigation · 2023Article
- Mineralocorticoid Receptor Antagonists for Preventing Chronic Kidney Disease Progression: Current Evidence and Future Challenges.International journal of molecular sciences · 2023Review
- The serine-threonine protein phosphatases that regulate the thiazide-sensitive NaCl cotransporter.Frontiers in physiology · 2023Review
- Tacrolimus Causes Hypertension by Increasing Vascular Contractility via RhoA (Ras Homolog Family Member A)/ROCK (Rho-Associated Protein Kinase) Pathway in Mice.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Kelch-like protein 3 in human disease and therapy.Molecular biology reports · 2022Review
- Potassium homeostasis: sensors, mediators, and targets.Pflugers Archiv : European journal of physiology · 2022Review
- Calcineurin in development and disease.Genes & diseases · 2022Review
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Calcineurin is a calcium/calmodulin-regulated phosphatase known for its role in activation of T cells following engagement of the T cell receptor. Calcineurin inhibitors (CNIs) are widely used as immunosuppressive agents; common adverse effects of CNIs are hypertension and hyperkalemia. While previous studies have implicated activation of the Na-Cl cotransporter (NCC) in the renal distal convoluted tubule (DCT) in this toxicity, the molecular mechanism of this effect is unknown. The renal effects of CNIs mimic the hypertension and hyperkalemia that result from germ-line mutations in with-no-lysine (WNK) kinases and the Kelch-like 3 (KLHL3)-CUL3 ubiquitin ligase complex. WNK4 is an activator of NCC and is degraded by binding to KLHL3 followed by WNK4's ubiquitylation and proteasomal degradation. This binding is prevented by phosphorylation of KLHL3 at serine 433 (KLHL3
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