FGF-21/FGF-21 receptor interaction and activation is determined by βKlotho
FGF-21/FGF-21 receptor interaction and activation is determined by βKlotho
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DOI：
10.1002/jcp.21357
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发表时间：
2008-04-01
影响因子：
5.6
通讯作者：
Shanafelt, Armen B.
中科院分区：
文献类型：
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作者：
Kharitonenkov, Alexei;Dunbar, James D.;Shanafelt, Armen B.
成纤维细胞生长因子-21（FGF-21）是一种代谢调节因子，可影响糖尿病啮齿动物和灵长类动物的血糖和血脂控制。我们证明β Klotho是活化的FGF-21-β Klotho-FGF受体（FGFR）复合物的组成部分，因此是FGF-21受体的关键亚基。缺乏β Klotho的细胞对FGF-21没有反应;向这些细胞中引入PKI β赋予FGF-21反应性，并概括了在天然反应细胞中观察到的FGF-21信号传导的整个范围。有趣的是，FGF-21介导的作用是肝素独立的，表明β Klotho在FGF-21活性中的作用与肝素在常规FGF信号传导中的作用相似。此外，除了赋予FGF-21特异性之外，β Klotho似乎支持FGF-19活性并介导FGF-19的受体选择性特征。总之，这些结果表明β Klotho和FGFR形成同源FGF-21受体复合物，介导FGF-21细胞特异性和生理作用。
Fibroblast growth factor-21 (FGF-2 1) is a metabolic regulator that can influence glucose and lipid control in diabetic rodents and primates. We demonstrate that beta Klotho is an integral part of an activated FGF-21-beta Klotho-FGF receptor (FGFR) complex thus a critical subunit of the FGF-21 receptor. Cells lacking beta Klotho did not respond to FGF-21; the introduction of PKIotho to these cells conferred FGF-21-responsiveness and recapitulated the entire scope of FGF-21 signaling observed in naturally responsive cells. Interestingly, FGF-21-mediated effects are heparin independent suggesting that beta Klotho plays a role in FGF-21 activity similar to the one played by heparin in the signaling of conventional FGFs. Moreover, in addition to conferring specificity for FGF-2 1, beta Klotho appears to support FGF-19 activity and mediates the receptor selectivity profile of FGF-19. All together, these results indicate that beta Klothoand FGFRs form the cognate FGF-21 receptor complex, mediating FGF-21 cellular specificity and physiological effects.