The Klotho gene family as a regulator of endocrine fibroblast growth factors.
The Klotho gene encodes a single-pass transmembrane protein and functions as an aging-suppressor gene, which extends lifespan when overexpressed and accelerates the development of aging-like phenotypes when disrupted in mice. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate and vitamin D homeostasis. It has been shown that Klotho-deficient mice and Fgf23 knockout mice exhibit identical phenotypes. This observation led to the identification of Klotho as a cofactor essential for interactions between FGF23 and FGF receptors. In addition to the Klotho-FGF23 axis, recent studies has shown that betaKlotho, a Klotho family protein, also functions as a cofactor required for FGF19 and FGF21 signaling and determines the tissue-specific metabolic activities of FGF19 and FGF21. This review summarizes recent progress in understanding of Klotho and betaKlotho function in the regulation of tissue-specific metabolic activity of the endocrine fibroblast growth factors (FGF19, FGF21, and FGF23).
Kurosu
Hiroshi
H
Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. kurosu78@research.twmu.ac.jp
Kuro-O
Makoto
M
D000818:Animals; D004702:Endocrine Glands / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005966:Glucuronidase / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000090265:Klotho Proteins; D008954:Models, Biological; D005810:Multigene Family / Q000502:physiology; D009928:Organ Specificity / Q000235:genetics; D010710:Phosphates / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014807:Vitamin D / Q000378:metabolism
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins