ArticleThe Journal of clinical investigation2011
IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 111 citations in OpenAlex.
- Review
- Role of serine/threonine phosphatases 1 and 2A in pancreatic acinar fluid and electrolyte secretion.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Pancreatitis: correcting CFTR expression and function as a promising effective treatment.Frontiers in physiology · 2026Review
- Beyond the mutations: spatiotemporal regulation of CFTR by cAMP and calcium signaling in epithelial physiology and cystic fibrosis.Cellular & molecular biology letters · 2025Review
- The function of chloride channels in digestive system disease (Review).International journal of molecular medicine · 2025Review
- Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium.Cellular & molecular biology letters · 2024Article
- Multiple Regulatory Signals and Components in the Modulation of Bicarbonate Transporters.Pharmaceutics · 2024Review
- Synergistic effects of agonists and two-pore-domain potassium channels on secretory responses of human pancreatic duct cells Capan-1.Pflugers Archiv : European journal of physiology · 2023Article
- The serine-threonine protein phosphatases that regulate the thiazide-sensitive NaCl cotransporter.Frontiers in physiology · 2023Review
- KFrontiers in cellular neuroscience · 2023Article
- WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia.American journal of respiratory cell and molecular biology · 2022Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- Association of genetic variants of oxidative stress responsive kinase 1 (OXSR1) with asthma exacerbations in non-smoking asthmatics.BMC pulmonary medicine · 2022Article
- Review
- Activation of the Ae4 (Slc4a9) cation-driven ClAmerican journal of physiology. Gastrointestinal and liver physiology · 2021Article
- The discovery and development of IP3 receptor modulators: an update.Expert opinion on drug discovery · 2021Article
- Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells.Pharmaceutics · 2020Article
- CaCold Spring Harbor perspectives in biology · 2020Review
- 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
- Regulation of CFTR Bicarbonate Channel Activity by WNK1: Implications for Pancreatitis and CFTR-Related Disorders.Cellular and molecular gastroenterology and hepatology · 2020Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Fluid and HCO(3)(-) secretion are fundamental functions of epithelia and determine bodily fluid volume and ionic composition, among other things. Secretion of ductal fluid and HCO(3)(-) in secretory glands is fueled by Na(+)/HCO(3)(-) cotransport mediated by basolateral solute carrier family 4 member 4 (NBCe1-B) and by Cl(-)/HCO(3)(-) exchange mediated by luminal solute carrier family 26, member 6 (Slc26a6) and CFTR. However, the mechanisms governing ductal secretion are not known. Here, we have shown that pancreatic ductal secretion in mice is suppressed by silencing of the NBCe1-B/CFTR activator inositol-1,4,5-trisphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT) and by inhibition of protein phosphatase 1 (PP1). In contrast, silencing the with-no-lysine (WNK) kinases and Ste20-related proline/alanine-rich kinase (SPAK) increased secretion. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression. IRBIT opposed the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities. Silencing of SPAK and IRBIT in the same ducts rescued ductal secretion due to silencing of IRBIT alone. These findings stress the pivotal role of IRBIT in epithelial fluid and HCO(3)(-) secretion and provide a molecular mechanism by which IRBIT coordinates these processes. They also have implications for WNK/SPAK kinase-regulated processes involved in systemic fluid homeostasis, hypertension, and cystic fibrosis.
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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 Socratic graph.