FGF23 is processed by proprotein convertases but not by PHEX

Anna Benet-Pagès, Bettina Lorenz-Depiereux, Hans Zischka, Kenneth E. White, Michael J. Econs, Tim M. Strom

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

X-linked hypophosphatemia (XLH) and autosomal dominant hypophosphatemic rickets (ADHR) are characterized by renal phosphate wasting, rickets, and osteomalacia. ADHR is caused by gain of function mutations in the fibroblast growth factor 23 gene (FGF23). During secretion, FGF23 is processed at the C-terminus between amino acids 179 and 180. The cleavage site is mutated in ADHR, preventing processing of FGF23. Here, we show that FGF23 is likely to be cleaved by subtilisin-like proprotein convertases (SPC) as cleavage can be inhibited by a specific SPC inhibitor in HEK293 cells. SPCs, which are widely expressed, were demonstrated to be also present in HEK293 cells as well as in osteoblasts. XLH is caused by loss of function mutations in the putative endopeptidase PHEX. It was tempting to speculate that FGF23 is a substrate of PHEX, but studies have been inconclusive so far. Here, we used a secreted form of PHEX (secPHEX) and tagged and untagged FGF23 constructs for co-incubation experiments. These experiments provided evidence against cleavage of intact FGF23 25-251 as well as of N-terminal (FGF23 25-179) and C-terminal (FGF23 180-251) fragments by the endopeptidase PHEX.

Original languageEnglish (US)
Pages (from-to)455-462
Number of pages8
JournalBone
Volume35
Issue number2
DOIs
StatePublished - Aug 1 2004

Fingerprint

Proprotein Convertases
Pseudogenes
Familial Hypophosphatemic Rickets
Genes
Endopeptidases
HEK293 Cells
fibroblast growth factor 23
Osteomalacia
Rickets
Mutation
Osteoblasts
Phosphates
Kidney
Amino Acids

Keywords

  • FGF23
  • Hypophosphatemia
  • PHEX
  • Proprotein convertases

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Benet-Pagès, A., Lorenz-Depiereux, B., Zischka, H., White, K. E., Econs, M. J., & Strom, T. M. (2004). FGF23 is processed by proprotein convertases but not by PHEX. Bone, 35(2), 455-462. https://doi.org/10.1016/j.bone.2004.04.002

FGF23 is processed by proprotein convertases but not by PHEX. / Benet-Pagès, Anna; Lorenz-Depiereux, Bettina; Zischka, Hans; White, Kenneth E.; Econs, Michael J.; Strom, Tim M.

In: Bone, Vol. 35, No. 2, 01.08.2004, p. 455-462.

Research output: Contribution to journalArticle

Benet-Pagès, A, Lorenz-Depiereux, B, Zischka, H, White, KE, Econs, MJ & Strom, TM 2004, 'FGF23 is processed by proprotein convertases but not by PHEX', Bone, vol. 35, no. 2, pp. 455-462. https://doi.org/10.1016/j.bone.2004.04.002
Benet-Pagès A, Lorenz-Depiereux B, Zischka H, White KE, Econs MJ, Strom TM. FGF23 is processed by proprotein convertases but not by PHEX. Bone. 2004 Aug 1;35(2):455-462. https://doi.org/10.1016/j.bone.2004.04.002
Benet-Pagès, Anna ; Lorenz-Depiereux, Bettina ; Zischka, Hans ; White, Kenneth E. ; Econs, Michael J. ; Strom, Tim M. / FGF23 is processed by proprotein convertases but not by PHEX. In: Bone. 2004 ; Vol. 35, No. 2. pp. 455-462.
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