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FGF23 Synthesis and Activity

  • Molecular Control of Phosphorus Homeostasis (B van der Eerden, Section Editor)
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Abstract

Purpose of Review

The phosphaturic hormone FGF23 is produced primarily in osteoblasts/osteocytes and is known to respond to increases in serum phosphate and 1,25(OH)2 vitamin D (1,25D). Novel regulators of FGF23 were recently identified and may help explain the pathophysiologies of several diseases. This review will focus on recent studies examining the synthesis and actions of FGF23.

Recent Findings

The synthesis of FGF23 in response to 1,25D is similar to other steroid hormone targets, but the cellular responses to phosphate remain largely unknown. The activity of intracellular processing genes control FGF23 glycosylation and phosphorylation, providing critical functions in determining the serum levels of bioactive FGF23. The actions of FGF23 largely occur through its co-receptor αKlotho (KL) under normal circumstances, but FGF23 has KL-independent activity during situations of high concentrations.

Summary

Recent work regarding FGF23 synthesis and bioactivity, as well as considerations for diseases of altered phosphate balance, will be reviewed.

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Papers of particular interest, published recently, have been highlighted as:•• Of major importance

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Acknowledgements

KEW receives royalties for licensing the FGF23 gene to Kyowa Hakko Kirin, Ltd.; the authors would like to acknowledge support by NIH grants DK112958, DK095784, and AR059278 (KEW), and T32-HL007910 (MLN).

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  1. Department of Medical & Molecular Genetics, Indiana University School of Medicine, 975 West Walnut St., IB130, Indianapolis, IN, 46202, USA

    Megan L. Noonan & Kenneth E. White

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Noonan, M.L., White, K.E. FGF23 Synthesis and Activity. Curr Mol Bio Rep 5, 18–25 (2019). https://doi.org/10.1007/s40610-019-0111-8

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