ArticleMolecular and cellular biology2012
Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligands.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 81 citations in OpenAlex.
- Can salivary phosphate levels be an early biomarker to monitor the evolvement of obesity?Contributions to nephrology · 2013Trial
- High-Fat Diet Differentially Regulates Fibroblast Growth Factor Expression in Metabolic Tissues of Young and Aged Male Mice.Journal of the Endocrine Society · 2025Article
- Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans WithJournal of the Endocrine Society · 2024Article
- Protein interaction networks characterizing the A549 cells Klotho transfected are associated with activated pro-apoptotic Bim and suppressed Wnt/β-catenin signaling pathway.Scientific reports · 2024Article
- Fibroblast growth factor signaling in axons: from development to disease.Cell communication and signaling : CCS · 2023Review
- Structural basis for FGF hormone signalling.Nature · 2023Article
- The role of fibroblast growth factor 18 in cancers: functions and signaling pathways.Frontiers in oncology · 2023Review
- Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System.Nutrients · 2022Review
- Interactions between FGF23 and vitamin D.Endocrine connections · 2022Review
- Soluble α-klotho and heparin modulate the pathologic cardiac actions of fibroblast growth factor 23 in chronic kidney disease.Kidney international · 2022Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Fibroblast growth factor receptor signalling dysregulation and targeting in breast cancer.Open biology · 2022Review
- FGF23 and Vitamin D Metabolism.JBMR plus · 2021Article
- Review
- The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair.Frontiers in cell and developmental biology · 2021Review
- Klotho: An Emerging Factor With Ergogenic Potential.Frontiers in rehabilitation sciences · 2021Review
- FGF/FGFR signaling in health and disease.Signal transduction and targeted therapy · 2020Review
- αKlotho-FGF23 interactions and their role in kidney disease: a molecular insight.Cellular and molecular life sciences : CMLS · 2019Review
- The FGF metabolic axis.Frontiers of medicine · 2019Review
- Structures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 5 countries.
Funding
Abstract
It has been recently established that Klotho coreceptors associate with fibroblast growth factor (FGF) receptor tyrosine kinases (FGFRs) to enable signaling by endocrine-acting FGFs. However, the molecular interactions leading to FGF-FGFR-Klotho ternary complex formation remain incompletely understood. Here, we show that in contrast to αKlotho, βKlotho binds its cognate endocrine FGF ligand (FGF19 or FGF21) and FGFR independently through two distinct binding sites. FGF19 and FGF21 use their respective C-terminal tails to bind to a common binding site on βKlotho. Importantly, we also show that Klotho coreceptors engage a conserved hydrophobic groove in the immunoglobulin-like domain III (D3) of the "c" splice isoform of FGFR. Intriguingly, this hydrophobic groove is also used by ligands of the paracrine-acting FGF8 subfamily for receptor binding. Based on this binding site overlap, we conclude that while Klotho coreceptors enhance binding affinity of FGFR for endocrine FGFs, they actively suppress binding of FGF8 subfamily ligands to FGFR.
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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.