描述：
Fibroblast growth factor 23 (FGF-23) is a 30 32 kDa member of the FGF gene family.
Based on its structure, it is further classified as an FGF-19 subfamily member. This subfamily
includes FGF-19, -21, and -23. Like all other FGF subfamilies, FGF-19 subfamily members
contain a 120 amino acid (aa) core FGF domain that exhibits a β-trefoil structure. Unlike
other FGF subfamilies, FGF-19 subfamily members exist as highly diffusible molecules that is
attributed to poor ECM/heparin sulfate binding. The cDNA for mouse FGF-23 predicts a 251
aa polypeptide that contains a 24 aa signal sequence and a 227 aa mature region. Mature
mouse FGF-23 shows 72% aa identity to human FGF-23.The FGF-19 subfamily shares an
unusual receptor configuration. The standard model for FGFsignaling requires an FGF:FGFR:
heparin sulfate complex. Given FGF-23’s minimal association with heparin, a substitute
termed (α) Klotho has evolved that serves the same function. Although FGF-23 binds to the
widely expressed “c” isoforms of FGFR1 and 3 plus FGFR4, Klotho has a restricted distribution
that limits FGF-23 activity. It should be noted that heparindependency has been reported for
FGF-19 signaling, and this observation may extend to FGF-23. The FGF-19 subfamily is
considered endocrine in nature. All three subfamily members impact some aspect of
metabolism and all three are induced by a nuclear receptor heterodimer that includes the
retinoid X receptor. FGF-23 is considered a phosphatonin; that is, a molecule that reduces
circulating plasma phosphate. It is produced by osteocytes and osteoblasts in response to high
circulating phosphate levels, elevated parathyroid hormone that induces hypercalcemia, and
circulatory volume loading. Upon binding to FGF-23 receptors on renal proximal tubular
epithelium, two basic changes are seen. First, the enzyme responsible for generating the
active form of vitamin D is suppressed, resulting in decreased levels of bioactive vitamin D.
Since vitamin D promotes intestinal phosphate absorption, plasma phosphate declines. Second,
the transporters responsible for phosphate resorption on renal epithelium are down regulated,
resulting in decreased uptake from urine and again a decline in blood phosphorus.
原厂资料：
Fibroblast growth factor 23 (FGF-23) is a 30 32 kDa member of the FGF gene family.
Based on its structure, it is further classified as an FGF-19 subfamily member. This subfamily
includes FGF-19, -21, and -23. Like all other FGF subfamilies, FGF-19 subfamily members
contain a 120 amino acid (aa) core FGF domain that exhibits a β-trefoil structure. Unlike
other FGF subfamilies, FGF-19 subfamily members exist as highly diffusible molecules that is
attributed to poor ECM/heparin sulfate binding. The cDNA for mouse FGF-23 predicts a 251
aa polypeptide that contains a 24 aa signal sequence and a 227 aa mature region. Mature
mouse FGF-23 shows 72% aa identity to human FGF-23.The FGF-19 subfamily shares an
unusual receptor configuration. The standard model for FGFsignaling requires an FGF:FGFR:
heparin sulfate complex. Given FGF-23’s minimal association with heparin, a substitute
termed (α) Klotho has evolved that serves the same function. Although FGF-23 binds to the
widely expressed “c” isoforms of FGFR1 and 3 plus FGFR4, Klotho has a restricted distribution
that limits FGF-23 activity. It should be noted that heparindependency has been reported for
FGF-19 signaling, and this observation may extend to FGF-23. The FGF-19 subfamily is
considered endocrine in nature. All three subfamily members impact some aspect of
metabolism and all three are induced by a nuclear receptor heterodimer that includes the
retinoid X receptor. FGF-23 is considered a phosphatonin; that is, a molecule that reduces
circulating plasma phosphate. It is produced by osteocytes and osteoblasts in response to high
circulating phosphate levels, elevated parathyroid hormone that induces hypercalcemia, and
circulatory volume loading. Upon binding to FGF-23 receptors on renal proximal tubular
epithelium, two basic changes are seen. First, the enzyme responsible for generating the
active form of vitamin D is suppressed, resulting in decreased levels of bioactive vitamin D.
Since vitamin D promotes intestinal phosphate absorption, plasma phosphate declines. Second,
the transporters responsible for phosphate resorption on renal epithelium are down regulated,
resulting in decreased uptake from urine and again a decline in blood phosphorus.
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