Regulation of fibroblast growth factor-23 signaling by Klotho

Hiroshi Kurosu; Yasushi Ogawa; Masayoshi Miyoshi; Masaya Yamamoto; Animesh Nandi; Kevin P. Rosenblatt; Michel G Baum; Susan Schiavi; Ming C Hu; Orson W Moe; Makoto Kuro-o

doi:10.1074/jbc.C500457200

Regulation of fibroblast growth factor-23 signaling by Klotho

Hiroshi Kurosu, Yasushi Ogawa, Masayoshi Miyoshi, Masaya Yamamoto, Animesh Nandi, Kevin P. Rosenblatt, Michel G Baum, Susan Schiavi, Ming C Hu, Orson W Moe, Makoto Kuro-o

Research output: Contribution to journal › Article › peer-review

1119 Scopus citations

Abstract

The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.

Original language	English (US)
Pages (from-to)	6120-6123
Number of pages	4
Journal	Journal of Biological Chemistry
Volume	281
Issue number	10
DOIs	https://doi.org/10.1074/jbc.C500457200
State	Published - Mar 10 2006

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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title = "Regulation of fibroblast growth factor-23 signaling by Klotho",

abstract = "The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.",

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AU - Kurosu, Hiroshi

AU - Ogawa, Yasushi

AU - Miyoshi, Masayoshi

AU - Yamamoto, Masaya

AU - Nandi, Animesh

AU - Rosenblatt, Kevin P.

AU - Baum, Michel G

AU - Schiavi, Susan

AU - Hu, Ming C

AU - Moe, Orson W

AU - Kuro-o, Makoto

PY - 2006/3/10

Y1 - 2006/3/10

N2 - The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.

AB - The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.

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Regulation of fibroblast growth factor-23 signaling by Klotho

Abstract

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