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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-12-29
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1873-3468
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pubmed:author |
pubmed-author:BelouskiEdE,
pubmed-author:ChenChingC,
pubmed-author:FisherSethS,
pubmed-author:HawkinsNessaN,
pubmed-author:HechtRandyR,
pubmed-author:LiYue-ShengYS,
pubmed-author:LindbergRichardR,
pubmed-author:MichaelsMark LML,
pubmed-author:NoseNN,
pubmed-author:PatelJenniferJ,
pubmed-author:SmithSteveS,
pubmed-author:SteavensonShirleyS,
pubmed-author:StevensJennitteJ,
pubmed-author:VéniantMurielleM,
pubmed-author:VighB JBJ,
pubmed-author:WangMinghanM,
pubmed-author:WintersDwightD,
pubmed-author:XuJingJ,
pubmed-author:YieJunmingJ
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pubmed:issnType |
Electronic
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pubmed:day |
5
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pubmed:volume |
583
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19-24
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pubmed:dateRevised |
2010-5-26
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pubmed:meshHeading |
pubmed-meshheading:19059246-Amino Acid Sequence,
pubmed-meshheading:19059246-Cell Line,
pubmed-meshheading:19059246-Fibroblast Growth Factors,
pubmed-meshheading:19059246-Genes, Reporter,
pubmed-meshheading:19059246-Humans,
pubmed-meshheading:19059246-Luciferases,
pubmed-meshheading:19059246-Membrane Proteins,
pubmed-meshheading:19059246-Molecular Sequence Data,
pubmed-meshheading:19059246-Protein Structure, Tertiary,
pubmed-meshheading:19059246-Receptor, Fibroblast Growth Factor, Type 1
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pubmed:year |
2009
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pubmed:articleTitle |
FGF21 N- and C-termini play different roles in receptor interaction and activation.
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pubmed:affiliation |
Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, CA 91320, USA. jyie@amgen.com
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pubmed:publicationType |
Journal Article
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