Regulation of fibroblast growth factor-23 signaling by Klotho
Regulation of fibroblast growth factor-23 signaling by Klotho
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DOI：
10.1074/jbc.c500457200
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发表时间：
2006-03-10
影响因子：
4.8
通讯作者：
Kuro-o, M
中科院分区：
文献类型：
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作者：
Kurosu, H;Ogawa, Y;Kuro-o, M
衰老抑制基因 Klotho 编码单次跨膜蛋白。 Klotho 缺陷小鼠表现出多种衰老样表型，其中许多与成纤维细胞生长因子 23 (FGF23) 缺陷小鼠中观察到的相似。为了测试 Klotho 和 FGF23 可能在共同信号转导途径中发挥作用的可能性，我们研究了 Klotho 是否参与 FGF 信号转导。在这里，我们证明 Klotho 蛋白直接结合多个 FGF 受体 (FGFR)。 Klotho-FGFR 复合物以比单独的 FGFR 或 Klotho 更高的亲和力与 FGF23 结合。此外，Klotho还显着增强了FGF23诱导各类细胞中FGF受体底物和ERK磷酸化的能力。因此，Klotho 作为 FGF23 激活 FGF 信号传导所必需的辅助因子发挥作用。
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.