Evidence map›Paper›PMID 25195776›Full record

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.

Iris Lindberg, Hong Weng Pang, Joseph P Stains, David Clark, Austin J Yang, Lynda Bonewald, Kevin Z Li

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. 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 · 2021
    Article
  6. Article
  7. FGF23 signalling and physiology.Journal of molecular endocrinology · 2021
    Review
  8. Upstream Regulators of Fibroblast Growth Factor 23.Frontiers in endocrinology · 2021
    Review
  9. Article
  10. Article
  11. The Role of Fibroblast Growth Factor 23 in Inflammation and Anemia.International journal of molecular sciences · 2019
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. The secretory pathway kinases.Biochimica et biophysica acta · 2015
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Iris LindbergDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Hong Weng Pang
Joseph P Stains
David Clark
Austin J Yang
Lynda Bonewald
Kevin Z Li
University of Maryland, Baltimore · USUniversity of Missouri–Kansas City · US

Funding

CONTROL OF PEPTIDE HORMONE BIOSYNTHESIS BY PC2 AND 7B2R01DK049703 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI LINDBERG, IRIS · 1996 to 2012
$3.7M
Spatial Control of Bone Remodeling by Gap Junction-Communicated cAMPR01AR063631 · NIAMS · UNIVERSITY OF MARYLAND BALTIMORE · PI STAINS, JOSEPH P. · 2013 to 2024
$3.3M
NIAMS NIH HHS R01 AR063631NIDDK NIH HHS DK49703-16NIDDK NIH HHS R01 DK049703
6 · The paper itself

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.

Indexed as

AnimalsBone and BonesCell LineFibroblast Growth Factor-23Fibroblast Growth FactorsHumansMiceMutagenesis, Site-DirectedPhosphorylationFGF23 protein, humanFgf23 protein, mouseFibroblast Growth Factor-23Fibroblast Growth FactorsBONEFAM20CFGF23KINASEOSTEOCYTEPHOSPHATE HOMEOSTASIS

Identifiers

PMID25195776
PMCPMC4750499
OpenAlexW1606943476

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.