Linked Life Data

19117008

Source:http://linkedlifedata.com/resource/pubmed/id/19117008

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-3-2
pubmed:abstractText
Fibroblast growth factor 21 is a member of endocrine FGFs subfamily, along with FGF19 and FGF23. It is emerging as a novel regulator with beneficial effects on a variety of metabolic parameters, including glucose and lipid control. FGF21 activity depends on membrane protein betaKlotho that physically complexes with various FGF receptors, thus conferring them the ability to bind FGF21 and activate downstream signaling pathways. FGF21, like other FGFs, folds to a beta-trefoil-like core region, with disordered N- and C-termini. In order to investigate their role in the activity of FGF21, we have constructed a series of deletion mutants and tested them for their ability to (1) bind betaKlotho, analyzed by surface plasmon resonance spectroscopy (2) signal through MAPK phosphorylation and inhibit apoptosis in 3T3-L1/betaKlotho fibroblasts (3) stimulate GLUT1 mRNA upregulation and glucose uptake in 3T3-L1 adipocytes. Binding studies with betaKlotho revealed that the interaction with the co-receptor involves the C-terminus, as progressive removal of amino acids from the carboxy end decreased affinity for betaKlotho. By contrast, removal of up to 17 amino acids from the N-terminus had no effect on the interaction with betaKlotho. Terminal deletions had greater effect on function, as deletions of six amino acids from the amino-terminus and only four from the carboxy-terminus each significantly impacted activity (10-fold). Of the extreme terminal truncations, with no detectable activity, DeltaN17 acted as competitive antagonist while DeltaC20 did not. Our structure/function studies show that the C-terminus is important for betaKlotho interaction whereas the N-terminus likely interacts directly with FGF receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1097-4652
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
219
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
227-34
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Different roles of N- and C- termini in the functional activity of FGF21.
pubmed:affiliation
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. micanovic_radmila@lilly.com
pubmed:publicationType
Journal Article