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

J Cell Physiol. 2008 Apr;215(1):1-7. doi: 10.1002/jcp.21357.


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.

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Protein Binding
  • Receptors, Fibroblast Growth Factor / metabolism*


  • Klb protein, mouse
  • Membrane Proteins
  • Receptors, Fibroblast Growth Factor
  • fibroblast growth factor 21
  • fibroblast growth factor-21 receptor, mouse
  • Fibroblast Growth Factors