ArticleJournal of the American Society of Nephrology : JASN2016
EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2-Mediated Renal Water Reabsorption.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- GLUT9b- and ABCG2-mediated collecting duct urate transport uncovers a vasopressin-independent mechanism of renal water reabsorption.The Journal of clinical investigation · 2026Article
- Expanding Mechanistic Insights into Urinary Concentrating Ability.Journal of the American Society of Nephrology : JASN · 2025Article
- The biology of water homeostasis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Ribosomal s6 kinase is a mediator of aquaporin-2 S256 phosphorylation and membrane accumulation after EGFR inhibition with erlotinib.American journal of physiology. Renal physiology · 2025Article
- Phosphoproteomic response to epidermal growth factor in native rat inner medullary collecting duct.American journal of physiology. Renal physiology · 2025Article
- Collecting duct water permeability inhibition by EGF is associated with decreased cAMP, PKA activity, and AQP2 phosphorylation at SerAmerican journal of physiology. Renal physiology · 2024Article
- Alteration of N6-methyladenosine epitranscriptome profiles in bilateral ureteral obstruction-induced obstructive nephropathy in juvenile rats.Pediatric research · 2023Article
- Intracellular sites of AQP2 S256 phosphorylation identified using inhibitors of the AQP2 recycling itinerary.American journal of physiology. Renal physiology · 2023Article
- Aquaporins in Diabetes Insipidus.Advances in experimental medicine and biology · 2023Article
- Aquaporins in Urinary System.Advances in experimental medicine and biology · 2023Article
- Identification of IQGAP1 as a SLC26A4 (Pendrin)-Binding Protein in the Kidney.Frontiers in molecular biosciences · 2022Article
- Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases.Nature reviews. Nephrology · 2021Review
- Actin-related protein 2/3 complex plays a critical role in the aquaporin-2 exocytotic pathway.American journal of physiology. Renal physiology · 2021Article
- Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting.JCI insight · 2021Article
- An AMPK activator as a therapeutic option for congenital nephrogenic diabetes insipidus.JCI insight · 2021Article
- The Role of Vasopressin V2 Receptor in Drug-Induced Hyponatremia.Frontiers in physiology · 2021Review
- Article
- Targeting the Trafficking of Kidney Water Channels for Therapeutic Benefit.Annual review of pharmacology and toxicology · 2020Review
- Arginine Vasopressin and Posterior Reversible Encephalopathy Syndrome Pathophysiology: the Missing Link?Molecular neurobiology · 2019Review
- Small molecules for modulating the localisation of the water channel aquaporin-2-disease relevance and perspectives for targeting local cAMP signalling.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Nephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been sought. Successful identification of compounds by our high-throughput chemical screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors stimulate AQP2 trafficking and reduce urine output. Erlotinib, a selective EGFR inhibitor, enhanced AQP2 apical membrane expression in collecting duct principal cells and reduced urine volume by 45% after 5 days of treatment in mice with lithium-induced NDI. Similar to VP, erlotinib increased exocytosis and decreased endocytosis in LLC-PK1 cells, resulting in a significant increase in AQP2 membrane accumulation. Erlotinib increased phosphorylation of AQP2 at Ser-256 and Ser-269 and decreased phosphorylation at Ser-261 in a dose-dependent manner. However, unlike VP, the effect of erlotinib was independent of cAMP, cGMP, and protein kinase A. Conversely, EGF reduced VP-induced AQP2 Ser-256 phosphorylation, suggesting crosstalk between VP and EGF in AQP2 trafficking and a role of EGF in water homeostasis. These results reveal a novel pathway that contributes to the regulation of AQP2-mediated water reabsorption and suggest new potential therapeutic strategies for NDI treatment.
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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.