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The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled.
Cell Biochem Funct. 2012 Jul; 30(5):355-75.CB

Abstract

The eggshell is an ancient innovation that helped the vertebrates' transition from the oceans and gain dominion over the land. Coincident with this conquest, several new eggshell and noncollagenous bone-matrix proteins (NCPs) emerged. The protein ovocleidin-116 is one of these proteins with an ancestry stretching back to the Triassic. Ovocleidin-116 is an avian homolog of Matrix Extracellular Phosphoglycoprotein (MEPE) and belongs to a group of proteins called Small Integrin-Binding Ligand Interacting Glycoproteins (SIBLINGs). The genes for these NCPs are all clustered on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of the SIBLING proteins is an Acidic Serine Aspartate-Rich MEPE (ASARM)-associated motif. The ASARM motif and the released ASARM peptide play roles in mineralization, bone turnover, mechanotransduction, phosphate regulation and energy metabolism. ASARM peptides and motifs are physiological substrates for phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), a Zn metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets. PHEX interacts with another ASARM motif containing SIBLING protein, Dentin Matrix Protein-1 (DMP1). DMP1 mutations cause bone-renal defects that are identical with the defects caused by loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both X-linked hypophosphatemic rickets and ARHR, increased fibroblast growth factor 23 (FGF23) expression occurs, and activating mutations in FGF23 cause autosomal dominant hypophosphatemic rickets (ADHR). ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. This review will discuss the evidence for a new integrative pathway involved in bone formation, bone-renal mineralization, renal phosphate homeostasis and energy metabolism in disease and health.

Authors+Show Affiliations

Department of Internal Medicine, The Kidney Institute, Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS, USA. prowe@kumc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

22573484

Citation

Rowe, Peter S N.. "The Chicken or the Egg: PHEX, FGF23 and SIBLINGs Unscrambled." Cell Biochemistry and Function, vol. 30, no. 5, 2012, pp. 355-75.
Rowe PS. The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled. Cell Biochem Funct. 2012;30(5):355-75.
Rowe, P. S. (2012). The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled. Cell Biochemistry and Function, 30(5), 355-75. https://doi.org/10.1002/cbf.2841
Rowe PS. The Chicken or the Egg: PHEX, FGF23 and SIBLINGs Unscrambled. Cell Biochem Funct. 2012;30(5):355-75. PubMed PMID: 22573484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled. A1 - Rowe,Peter S N, Y1 - 2012/05/09/ PY - 2012/01/04/received PY - 2012/03/23/revised PY - 2012/04/18/accepted PY - 2012/5/11/entrez PY - 2012/5/11/pubmed PY - 2014/5/16/medline SP - 355 EP - 75 JF - Cell biochemistry and function JO - Cell Biochem. Funct. VL - 30 IS - 5 N2 - The eggshell is an ancient innovation that helped the vertebrates' transition from the oceans and gain dominion over the land. Coincident with this conquest, several new eggshell and noncollagenous bone-matrix proteins (NCPs) emerged. The protein ovocleidin-116 is one of these proteins with an ancestry stretching back to the Triassic. Ovocleidin-116 is an avian homolog of Matrix Extracellular Phosphoglycoprotein (MEPE) and belongs to a group of proteins called Small Integrin-Binding Ligand Interacting Glycoproteins (SIBLINGs). The genes for these NCPs are all clustered on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of the SIBLING proteins is an Acidic Serine Aspartate-Rich MEPE (ASARM)-associated motif. The ASARM motif and the released ASARM peptide play roles in mineralization, bone turnover, mechanotransduction, phosphate regulation and energy metabolism. ASARM peptides and motifs are physiological substrates for phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), a Zn metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets. PHEX interacts with another ASARM motif containing SIBLING protein, Dentin Matrix Protein-1 (DMP1). DMP1 mutations cause bone-renal defects that are identical with the defects caused by loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both X-linked hypophosphatemic rickets and ARHR, increased fibroblast growth factor 23 (FGF23) expression occurs, and activating mutations in FGF23 cause autosomal dominant hypophosphatemic rickets (ADHR). ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. This review will discuss the evidence for a new integrative pathway involved in bone formation, bone-renal mineralization, renal phosphate homeostasis and energy metabolism in disease and health. SN - 1099-0844 UR - https://www.unboundmedicine.com/medline/citation/22573484/The_chicken_or_the_egg:_PHEX_FGF23_and_SIBLINGs_unscrambled_ L2 - https://doi.org/10.1002/cbf.2841 DB - PRIME DP - Unbound Medicine ER -