Regulation of Fibroblast Growth Factor-23 Signaling by Klotho
| Autor: | Makoto Kuro-o, Orson W. Moe, Masayoshi Miyoshi, Ming Chang Hu, Yasushi Ogawa, Hiroshi Kurosu, Masaya Yamamoto, Susan C. Schiavi, Animesh Nandi, Kevin P. Rosenblatt, Michel Baum |
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| Rok vydání: | 2006 |
| Předmět: |
MAPK/ERK pathway
Biology urologic and male genital diseases Fibroblast growth factor PC12 Cells Biochemistry Article Cell Line Mice Animals Humans Klotho Proteins Molecular Biology Klotho Glucuronidase Mice Knockout Cell Biology Fibroblast growth factor receptor 4 Fibroblast growth factor receptor 3 Receptors Fibroblast Growth Factor female genital diseases and pregnancy complications Rats Cell biology Fibroblast Growth Factors Fibroblast Growth Factor-23 stomatognathic diseases Fibroblast growth factor receptor Cancer research Phosphorylation Signal transduction HeLa Cells Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 281:6120-6123 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.c500457200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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