ArticleJCI insight2019
A G protein-coupled, IP3/protein kinase C pathway controlling the synthesis of phosphaturic hormone FGF23.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation.Molecular metabolism · 2026Review
- Lysophosphatidic Acid Synergizes With 1,25-Dihydroxyvitamin D to Promote Fibroblast Growth Factor-23 Synthesis via MAPK Signaling and Induction of the IL12A Gene.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Comparative Transcriptomics Reveals the Molecular Basis for Inducer-Dependent Efficiency in Gastrodin Propionylation byBiomolecules · 2025Article
- TGFβ signaling regulates the response of the skeleton to phosphate.bioRxiv : the preprint server for biology · 2025Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Potential Targeting Mechanisms for Bone-Directed Therapies.International journal of molecular sciences · 2024Review
- Both enantiomers of β-aminoisobutyric acid BAIBA regulate Fgf23 via MRGPRD receptor by activating distinct signaling pathways in osteocytes.Cell reports · 2024Article
- Organic phosphate but not inorganic phosphate regulatesiScience · 2024Article
- Gα11 deficiency increases fibroblast growth factor 23 levels in a mouse model of familial hypocalciuric hypercalcemia.JCI insight · 2024Article
- PKC regulates αKlotho gene expression in MDCK and NRK-52E cells.Pflugers Archiv : European journal of physiology · 2024Article
- Review
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Review
- Regulation of FGF23: Beyond Bone.Current osteoporosis reports · 2021Review
- FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.International journal of molecular sciences · 2021Review
- MaternalFrontiers in genetics · 2021Article
- Gs/Gq signaling switch in β cells defines incretin effectiveness in diabetes.The Journal of clinical investigation · 2020Article
- New and Old Osteocytic Cell Lines and 3D Models.Current osteoporosis reports · 2020Review
- Osteocytic FGF23 and Its Kidney Function.Frontiers in endocrinology · 2020Review
- Extra-Large Gα Protein (XLαs) Deficiency Causes Severe Adenine-Induced Renal Injury with Massive FGF23 Elevation.Endocrinology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Dysregulated actions of bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) result in several inherited diseases, such as X-linked hypophosphatemia (XLH), and contribute substantially to the mortality in kidney failure. Mechanisms governing FGF23 production are poorly defined. We herein found that ablation of the Gq/11α-like, extralarge Gα subunit (XLαs), a product of GNAS, exhibits FGF23 deficiency and hyperphosphatemia in early postnatal mice (XLKO). FGF23 elevation in response to parathyroid hormone, a stimulator of FGF23 production via cAMP, was intact in XLKO mice, while skeletal levels of protein kinase C isoforms α and δ (PKCα and PKCδ) were diminished. XLαs ablation in osteocyte-like Ocy454 cells suppressed the levels of FGF23 mRNA, inositol 1,4,5-trisphosphate (IP3), and PKCα/PKCδ proteins. PKC activation in vivo via injecting phorbol myristate acetate (PMA) or by constitutively active Gqα-Q209L in osteocytes and osteoblasts promoted FGF23 production. Molecular studies showed that the PKC activation-induced FGF23 elevation was dependent on MAPK signaling. The baseline PKC activity was elevated in bones of Hyp mice, a model of XLH. XLαs ablation significantly, but modestly, reduced serum FGF23 and elevated serum phosphate in Hyp mice. These findings reveal a potentially hitherto-unknown mechanism of FGF23 synthesis involving a G protein-coupled IP3/PKC pathway, which may be targeted to fine-tune FGF23 levels.
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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.