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Kharitonenkov, A. et al.

Alexei Kharitonenkov, 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,

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

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.[1]

References

FGF-21/FGF-21 receptor interaction and activation is determined by betaKlotho. Kharitonenkov, A., Dunbar, J.D., Bina, H.A., Bright, S., Moyers, J.S., Zhang, C., Ding, L., Micanovic, R., Mehrbod, S.F., Knierman, M.D., Hale, J.E., Coskun, T., Shanafelt, A.B. J. Cell. Physiol. (2008) [Pubmed]

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