Regulation of Fibroblast Growth Factor-23 Signaling by Klotho*

By H. Kurosu, Y. Ogawa, Masayoshi Miyoshi, Masaya Yamamoto, A. Nandi, K. Rosenblatt, M. Baum, S. Schiavi, M. Hu, O. Moe and 1 more. Journal of Biological Chemistry, 2006

1,332 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology, Nephrology

View Paper: https://www.semanticscholar.org/paper/5258b445013c59131d0609aa5f489f56e913938b

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Citations in the corpus

Klotho is a substrate for a-, - and ?-secretase (2009, methodology): “293Kl (HEK293 cells stably expressing flag-tagged Kl) were described [6].”
Programming the magnitude and persistence of antibody responses with innate immunity (2011, neutral): “vector RIG 0 2 4 6 vector KLm (1-1012) KLs (1-549) KLsss (34-549)”
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. (2010, background): “Of note, FGF21 and FGF23 action have already been linked to aging phenomena because the Klotho family of transmembrane “anti-aging” proteins was demonstrated to work as a crucial coreceptor for FGF-R signaling (199, 200).”
Deregulation of the Histone Lysine-Specific Demethylase 1 Is Involved in Human Hepatocellular Carcinoma (2019, background): “Klotho is essential for endogenous FGF23 function as it converts FGFR1c into a specific FGF23 receptor [5,6].”
Satellite cells and the muscle stem cell niche. (2013, background): “This possibility is supported by a recent finding that a Wnt binding protein, Klotho, is a circulating hormone and can affect tissue aging (281, 313).”