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09:16
Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
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Phosphate-Sensing
Yuichi Takashi1, Seiji Fukumoto2
1Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine, Fukuoka, Japan.
Advances in Experimental Medicine and Biology
|March 15, 2022
Summary
Bone senses high phosphate levels via FGFR1c, activating a pathway that increases FGF23 production to regulate blood phosphate. This discovery highlights a key feedback mechanism in phosphate homeostasis.
Area of Science:
- Biochemistry
- Endocrinology
- Molecular Biology
Background:
- Phosphate homeostasis is crucial, as imbalances cause diseases like tumoral calcinosis and rickets.
- Fibroblast growth factor 23 (FGF23) is the primary hormone regulating blood phosphate levels.
- The exact mechanisms by which bone senses phosphate and regulates FGF23 remain unclear.
Purpose of the Study:
- To elucidate the phosphate-sensing mechanisms in bone.
- To identify the molecular players involved in regulating FGF23 production in response to phosphate levels.
Main Methods:
- Investigated the effect of extracellular phosphate on FGF receptor 1c (FGFR1c) phosphorylation.
- Analyzed the downstream signaling pathway involving MEK/ERK.
- Examined the regulation of transcription factors and the GALNT3 gene.
Main Results:
- High extracellular phosphate phosphorylates FGFR1c.
- The MEK/ERK pathway regulates transcription factors and GALNT3 gene expression.
- The FGFR1c-GALNT3 axis enhances FGF23 production, suggesting FGFR1c acts as a phosphate sensor.
Conclusions:
- FGFR1c functions as a phosphate-sensing molecule in bone, regulating FGF23 production.
- A feedback loop involving FGFR1c and FGF23 is critical for blood phosphate regulation.
- Other phosphate-sensing mechanisms may involve PiT1, PiT2, and the calcium-sensing receptor.
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