FGF21 N- and C-termini play different roles in receptor interaction and activation - PubMed (original) (raw)

. 2009 Jan 5;583(1):19-24.

doi: 10.1016/j.febslet.2008.11.023. Epub 2008 Dec 4.

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

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FGF21 N- and C-termini play different roles in receptor interaction and activation

Junming Yie et al. FEBS Lett. 2009.

Free article

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.

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