| Literature DB >> 19059246 |
Junming Yie1, Randy Hecht, Jennifer Patel, Jennitte Stevens, Wei Wang, Nessa Hawkins, Shirley Steavenson, Steve Smith, Dwight Winters, Seth Fisher, Ling Cai, Ed Belouski, Ching Chen, Mark L Michaels, Yue-Sheng Li, Richard Lindberg, Minghan Wang, Murielle Véniant, Jing Xu.
Abstract
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.Entities:
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Year: 2008 PMID： 19059246 DOI： 10.1016/j.febslet.2008.11.023
Source DB: PubMed Journal: FEBS Lett ISSN： 0014-5793 Impact factor: 4.124