ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
FGF23 is endogenously phosphorylated in bone cells.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 38 citations in OpenAlex.
- Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation.Molecular metabolism · 2026Review
- A Novel Pathogenic Variant in Fibroblast Growth Factor 23 outside the Furin-Recognizing RXXR Motif in an Autosomal Dominant Hypophosphatemic Rickets Patient.Hormone research in paediatrics · 2025Article
- Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol.International journal of molecular sciences · 2022Article
- (Pro)renin Receptor Regulates Phosphate Homeostasis in RatsFrontiers in physiology · 2022Article
- Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Normal FGF23 Does Not Preclude Tumor-Induced Osteomalacia.JBMR plus · 2021Article
- FGF23 signalling and physiology.Journal of molecular endocrinology · 2021Review
- Upstream Regulators of Fibroblast Growth Factor 23.Frontiers in endocrinology · 2021Review
- IDG-SW3 Osteocyte Differentiation and Bone Extracellular Matrix Deposition Are Enhanced in a 3D Matrix Metalloproteinase-Sensitive Hydrogel.ACS applied bio materials · 2020Article
- Ancestral roles of the Fam20C family of secreted protein kinases revealed inThe Journal of cell biology · 2019Article
- The Role of Fibroblast Growth Factor 23 in Inflammation and Anemia.International journal of molecular sciences · 2019Review
- FGF23 Actions on Target Tissues-With and Without Klotho.Frontiers in endocrinology · 2018Review
- PAI-1 is a critical regulator of FGF23 homeostasis.Science advances · 2017Article
- Review
- Relationships between Bone Turnover and Energy Metabolism.Journal of diabetes research · 2017Review
- Extracellular Protein Phosphorylation, the Neglected Side of the Modification.Molecular & cellular proteomics : MCP · 2017Review
- Posttranslational processing of FGF23 in osteocytes during the osteoblast to osteocyte transition.Bone · 2016Article
- The secretory pathway kinases.Biochimica et biophysica acta · 2015Review
- Article
- A unified model for bone-renal mineral and energy metabolism.Current opinion in pharmacology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Levels of serum phosphate are controlled by the peptide hormone FGF23, secreted from bone osteocytes. Elevated levels of circulating FGF23 are a key factor in several hypophosphatemic disorders and play a role in chronic kidney disease. Posttranslational processing of FGF23 includes multi-site O-glycosylation, which reduces intracellular cleavage by proprotein convertases. The FGF23 protein also contains four serine phosphorylation consensus sequences (S-X-D/E); in this work, we asked whether FGF23 is a substrate for secretory phosphorylation. Both HEK cells as well as IDG-SW3 cells, an osteocyte model, incorporated radiolabeled orthophosphate into intact FGF23, as well as into the 14-kDa carboxy-terminal-but not the 17-kDa N-terminal-fragment. Sequential serine-to-alanine site-directed mutagenesis of four kinase consensus sites showed that labeling occurred on three serines within the carboxy-terminal fragment, Ser180 (adjacent to the cleavage site), Ser207, and Ser212. Liquid chromatography-coupled mass spectroscopy indicated the presence of phosphate at Ser212 in recombinant R&D mouse FGF23(R179Q) , confirming labeling results. A phosphopeptide-specific antibody was raised against phospho-Ser212 and exhibited immunoreactivity in osteocytes present in mouse long bone, providing further evidence that FGF23 is naturally phosphorylated in bone. Bone SIBLING proteins are serine-phosphorylated by the ubiquitous Golgi secretory kinase FAM20C. Cotransfection of HEK and MC3T3 cells with FGF23 and active, but not inactive, FAM20C kinase increased the storage and release of FGF23 in radiolabeling experiments, indicating potential effects of phosphorylation on FGF23 stability. Collectively, these data point to an important role for phosphorylation of FGF23 in bone.
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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.