FGF-21/FGF-21 receptor interaction and activation is determined by betaKlotho.

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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 Klotho is an integral part of an activated FGF-21-Klotho-FGF receptor (FGFR) complex thus a critical subunit of the FGF-21 receptor. Cells lacking Klotho did not respond to FGF-21; the introduction of Klotho 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 Klotho 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, Klotho appears to support FGF-19 activity and mediates the receptor selectivity profile of FGF-19. All together, these results indicate that Klotho and FGFRs form the cognate FGF-21 receptor complex, mediating FGF-21 cellular specificity and physiological effects. J. Cell. Physiol. 215: 1-7, 2008. 2007 Wiley-Liss, Inc.

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Animals Humans Mice 3T3-L1 Cells Fibroblast Growth Factors Membrane Proteins Receptors, Fibroblast Growth Factor Protein Binding