Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligands.

Détails

ID Serval
serval:BIB_1005546A5BA1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligands.
Périodique
Molecular and Cellular Biology
Auteur(s)
Goetz R., Ohnishi M., Ding X., Kurosu H., Wang L., Akiyoshi J., Ma J., Gai W., Sidis Y., Pitteloud N., Kuro-O M., Razzaque M.S., Mohammadi M.
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Statut éditorial
Publié
Date de publication
2012
Volume
32
Numéro
10
Pages
1944-1954
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
It has been recently established that Klotho coreceptors associate with fibroblast growth factor (FGF) receptor tyrosine kinases (FGFRs) to enable signaling by endocrine-acting FGFs. However, the molecular interactions leading to FGF-FGFR-Klotho ternary complex formation remain incompletely understood. Here, we show that in contrast to αKlotho, βKlotho binds its cognate endocrine FGF ligand (FGF19 or FGF21) and FGFR independently through two distinct binding sites. FGF19 and FGF21 use their respective C-terminal tails to bind to a common binding site on βKlotho. Importantly, we also show that Klotho coreceptors engage a conserved hydrophobic groove in the immunoglobulin-like domain III (D3) of the "c" splice isoform of FGFR. Intriguingly, this hydrophobic groove is also used by ligands of the paracrine-acting FGF8 subfamily for receptor binding. Based on this binding site overlap, we conclude that while Klotho coreceptors enhance binding affinity of FGFR for endocrine FGFs, they actively suppress binding of FGF8 subfamily ligands to FGFR.
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/06/2012 18:07
Dernière modification de la notice
20/08/2019 12:36
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