成纤维细胞生长因子21（FGF21）的N端和C端在受体相互作用及激活过程中发挥不同作用。
FGF21 N- and C-termini play different roles in receptor interaction and activation.
作者信息
Yie Junming, Hecht Randy, Patel Jennifer, Stevens Jennitte, Wang Wei, Hawkins Nessa, Steavenson Shirley, Smith Steve, Winters Dwight, Fisher Seth, Cai Ling, Belouski Ed, Chen Ching, Michaels Mark L, Li Yue-Sheng, Lindberg Richard, Wang Minghan, Véniant Murielle, Xu Jing
机构信息
Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, CA 91320, USA.
出版信息
FEBS Lett. 2009 Jan 5;583(1):19-24. doi: 10.1016/j.febslet.2008.11.023. Epub 2008 Dec 4.
Fibroblast growth factor-21 (FGF21) signaling requires the presence of beta-Klotho, a co-receptor with a very short cytoplasmic domain. Here we show that FGF21 binds directly to beta-Klotho through its C-terminus. Serial C-terminal truncations of FGF21 weakened or even abrogated its interaction with beta-Klotho in a Biacore assay, and led to gradual loss of potency in a luciferase reporter assay but with little effect on maximal response. In contrast, serial N-terminal truncations of FGF21 had no impact on beta-Klotho binding. Interestingly, several of them exhibited characteristics of partial agonists with minimal effects on potency. These data demonstrate that the C-terminus of FGF21 is critical for binding to beta-Klotho and the N-terminus is critical for fibroblast growth factor receptor (FGFR) activation.
成纤维细胞生长因子21（FGF21）信号传导需要β-klotho的存在，β-klotho是一种具有非常短细胞质结构域的共受体。在此我们表明，FGF21通过其C末端直接与β-klotho结合。在生物传感器分析中，FGF21的连续C末端截短削弱甚至消除了其与β-klotho的相互作用，并在荧光素酶报告基因分析中导致效力逐渐丧失，但对最大反应影响很小。相比之下，FGF21的连续N末端截短对β-klotho结合没有影响。有趣的是，其中一些表现出部分激动剂的特征，对效力影响最小。这些数据表明，FGF21的C末端对于与β-klotho结合至关重要，而N末端对于成纤维细胞生长因子受体（FGFR）激活至关重要。
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