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Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism.
Curr Opin Nephrol Hypertens. 2006 Jul; 15(4):437-41.CO

Abstract

PURPOSE OF REVIEW

This review summarizes the most recent findings on Klotho in the regulation of fibroblast growth factor-23 (FGF23) signaling and phosphate/calcium homeostasis.

RECENT FINDINGS

The klotho gene encodes a single-pass transmembrane protein and functions as an aging-suppressor gene, which extends life span when overexpressed and accelerates the development of aging-like phenotypes when disrupted in mice. FGF23 is a hormone that suppresses phosphate reabsorption in renal proximal tubules. Recent studies have shown that Klotho mice and Fgf23 mice exhibit identical phenotypes including hyperphosphatemia and hypercalcemia in addition to the aging-like syndrome. This may be explained by the fact that Klotho binds to multiple FGF receptors and increases their affinity to FGF23. Another Klotho protein function is to activate transient receptor potential vanilloid-5 - a calcium channel involved in calcium reabsorption in the kidney. Klotho protein can modify sugar chains on transient receptor potential vanilloid-5 through its activity as a beta-glucuronidase, preventing the calcium channel from internalization and inactivation.

SUMMARY

Klotho protein binds to fibroblast growth factor receptors and functions as a regulator of FGF23 signaling. It also functions as an enzyme that modifies sugar chains of transient receptor potential vanilloid-5 and regulates its activity. Klotho is a multi-functional protein that regulates phosphate/calcium metabolism as well as aging.

Authors+Show Affiliations

Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9072, USA. makoto.kuro-o@utsouthwestern.edu

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

16775459

Citation

Kuro-o, Makoto. "Klotho as a Regulator of Fibroblast Growth Factor Signaling and Phosphate/calcium Metabolism." Current Opinion in Nephrology and Hypertension, vol. 15, no. 4, 2006, pp. 437-41.
Kuro-o M. Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Curr Opin Nephrol Hypertens. 2006;15(4):437-41.
Kuro-o, M. (2006). Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Current Opinion in Nephrology and Hypertension, 15(4), 437-41.
Kuro-o M. Klotho as a Regulator of Fibroblast Growth Factor Signaling and Phosphate/calcium Metabolism. Curr Opin Nephrol Hypertens. 2006;15(4):437-41. PubMed PMID: 16775459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. A1 - Kuro-o,Makoto, PY - 2006/6/16/pubmed PY - 2006/12/9/medline PY - 2006/6/16/entrez SP - 437 EP - 41 JF - Current opinion in nephrology and hypertension JO - Curr Opin Nephrol Hypertens VL - 15 IS - 4 N2 - PURPOSE OF REVIEW: This review summarizes the most recent findings on Klotho in the regulation of fibroblast growth factor-23 (FGF23) signaling and phosphate/calcium homeostasis. RECENT FINDINGS: The klotho gene encodes a single-pass transmembrane protein and functions as an aging-suppressor gene, which extends life span when overexpressed and accelerates the development of aging-like phenotypes when disrupted in mice. FGF23 is a hormone that suppresses phosphate reabsorption in renal proximal tubules. Recent studies have shown that Klotho mice and Fgf23 mice exhibit identical phenotypes including hyperphosphatemia and hypercalcemia in addition to the aging-like syndrome. This may be explained by the fact that Klotho binds to multiple FGF receptors and increases their affinity to FGF23. Another Klotho protein function is to activate transient receptor potential vanilloid-5 - a calcium channel involved in calcium reabsorption in the kidney. Klotho protein can modify sugar chains on transient receptor potential vanilloid-5 through its activity as a beta-glucuronidase, preventing the calcium channel from internalization and inactivation. SUMMARY: Klotho protein binds to fibroblast growth factor receptors and functions as a regulator of FGF23 signaling. It also functions as an enzyme that modifies sugar chains of transient receptor potential vanilloid-5 and regulates its activity. Klotho is a multi-functional protein that regulates phosphate/calcium metabolism as well as aging. SN - 1062-4821 UR - https://www.unboundmedicine.com/medline/citation/16775459/Klotho_as_a_regulator_of_fibroblast_growth_factor_signaling_and_phosphate/calcium_metabolism_ L2 - https://doi.org/10.1097/01.mnh.0000232885.81142.83 DB - PRIME DP - Unbound Medicine ER -