Linked Life Data

15268897

Source:http://linkedlifedata.com/resource/pubmed/id/15268897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-7-22
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
8756-3282
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
455-62
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
FGF23 is processed by proprotein convertases but not by PHEX.
pubmed:affiliation
Institute of Human Genetics, GSF National Research Center, 85764 München-Neuherberg, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.