Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 284, Issue 4, Pages 977-981Publisher
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2001.5084
Keywords
FGF-23; PHEX; hypophosphatemia; phosphatonin; OOM; ADHR; XLH; osteomalacia; rickets
Categories
Funding
- NIDDK NIH HHS [R01 DK025409, R01 DK058546] Funding Source: Medline
Ask authors/readers for more resources
Oncogenic osteomalacia (OOM), X-linked hypophosphatemia (XLH), and autosomal dominant hypophosphatemic rickets (ADHR) are phenotypically similar disorders characterized by hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum calcitriol concentrations, normal serum concentrations of calcium and parathyroid hormone, and defective skeletal mineralization. XLH results from mutations in the PHEX gene, encoding a membrane-bound endopeptidase, whereas ADHR is associated with mutations of the gene encoding FGF-23. Recent evidence that FGF-23 is expressed in mesenchymal tumors associated with OOM suggests that FGF-23 is responsible for the phosphaturic activity previously termed phosphatonin. Here we show that both wildtype FGF-23 and the ADHR mutant, FGF-23(R179Q), inhibit phosphate uptake in renal epithelial cells. We further show that the endopeptidase, PHEX, degrades native FGF-23 but not the mutant form. Our results suggest that FGF-23 is involved in the pathogenesis of these three hypophosphatemic disorders and directly link PHEX and FGF-23 within the same biochemical pathway. (C) 2001 Academic Press.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available