| Literature DB >> 18064602 |
Alexei Kharitonenkov1, James D Dunbar, Holly A Bina, Stuart Bright, Julie S Moyers, Chen Zhang, Liyun Ding, Radmila Micanovic, Sean F Mehrbod, Michael D Knierman, John E Hale, Tamer Coskun, Armen B Shanafelt.
Abstract
Fibroblast growth factor-21 (FGF-21) is a metabolic regulator that can influence glucose and lipid control in diabetic rodents and primates. We demonstrate that betaKlotho is an integral part of an activated FGF-21-betaKlotho-FGF receptor (FGFR) complex thus a critical subunit of the FGF-21 receptor. Cells lacking betaKlotho did not respond to FGF-21; the introduction of betaKlotho to these cells conferred FGF-21-responsiveness and recapitulated the entire scope of FGF-21 signaling observed in naturally responsive cells. Interestingly, FGF-21-mediated effects are heparin independent suggesting that betaKlotho plays a role in FGF-21 activity similar to the one played by heparin in the signaling of conventional FGFs. Moreover, in addition to conferring specificity for FGF-21, betaKlotho appears to support FGF-19 activity and mediates the receptor selectivity profile of FGF-19. All together, these results indicate that betaKlotho and FGFRs form the cognate FGF-21 receptor complex, mediating FGF-21 cellular specificity and physiological effects. (c) 2007 Wiley-Liss, Inc.Entities:
Mesh：
Substances：
Year: 2008 PMID： 18064602 DOI： 10.1002/jcp.21357
Source DB: PubMed Journal: J Cell Physiol ISSN： 0021-9541 Impact factor: 6.384