Understanding the Physical Interactions in the FGF21/FGFR/β-Klotho Complex: Structural Requirements and Implications in FGF21 Signaling

Chemical Biology and Drug Design

Volumn 79, Issue 4, 2012, Pages 398-410

  Yie, Junming ^a   Wang, Wei ^a   Deng, Liying ^a   Tam, Lei Ting ^a   Stevens, Jennitte ^a   Chen, Michelle M ^a   Li, Yang ^a   Xu, Jing ^a   Lindberg, Richard ^a   Hecht, Randy ^a   Véniant, Murielle ^a   Chen, Ching ^a   Wang, Minghan ^a  

^a AMGEN INC   (United States)

Author keywords

Klotho; D1 and the D1 D2 linker; FGF21; FGFR1c

Indexed keywords

BETA KLOTHO PROTEIN; CELL RECEPTOR; FIBROBLAST GROWTH FACTOR 21; FIBROBLAST GROWTH FACTOR 21 FIBROBLAST GROWTH FACTO RECEPTOR BETA KLOTHO COMPLEX; FIBROBLAST GROWTH FACTOR RECEPTOR; KLOTHO PROTEIN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CELL SURFACE; COMPLEX FORMATION; DRUG RECEPTOR BINDING; FIELD FLOW FRACTIONATION; GENE DELETION; HUMAN; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN PROTEIN INTERACTION; PROTEIN QUATERNARY STRUCTURE;

CELL LINE; FIBROBLAST GROWTH FACTORS; HUMANS; MEMBRANE PROTEINS; PROTEIN INTERACTION DOMAINS AND MOTIFS; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; SIGNAL TRANSDUCTION;

EID: 84862782796     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2012.01325.x     Document Type: Article

References (29)

1. Fu L., John L.M., Adams S.H., Yu X.X., Tomlinson E., Renz M., Williams P.M. (2004) Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology;145:2594-2603.
2. Yu X., White K.E. (2005) FGF23 and disorders of phosphate homeostasis. Cytokine Growth Factor Rev;16:221-232.
3. Kharitonenkov A., Shiyanova T.L., Koester A., Ford A.M., Micanovic R., Galbreath E.J., Sandusky G.E. et al. (2005) FGF-21 as a novel metabolic regulator. J Clin Invest;115:1627-1635.
4. Kharitonenkov A., Shanafelt A.B. (2008) Fibroblast growth factor-21 as a therapeutic agent for metabolic diseases. BioDrugs;22:37-44.
5. Xu J., Stanislaus S., Chinookoswong N., Lau Y.Y., Hager T., Patel J., Ge H. et al. (2009) Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin resistant mouse models - association with liver and adipose tissue effects. Am J Physiol;297:E1105-E1114.
6. Xu J., Lloyd D.J., Hale C., Stanislaus S., Chen M., Sivits G., Vonderfecht S. et al. (2009) Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes;58:250-259.
7. Kharitonenkov A., Wroblewski V.J., Koester A., Chen Y.F., Clutinger C.K., Tigno X.T., Hansen B.C., Shanafelt A.B., Etgen G.J. (2007) The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology;148:774-781.
8. Goetz R., Beenken A., Ibrahimi O.A., Kalinina J., Olsen S.K., Eliseenkova A.V., Xu C. et al. (2007) Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members. Mol Cell Biol;27:3417-3428.
9. Kurosu H., Kuro O.M. (2009) The Klotho gene family as a regulator of endocrine fibroblast growth factors. Mol Cell Endocrinol;299:72-78.
10. Urakawa I., Yamazaki Y., Shimada T., Iijima K., Hasegawa H., Okawa K., Fujita T., Fukumoto S., Yamashita T. et al. (2006) Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature;444:770-774.
11. Ogawa Y., Kurosu H., Yamamoto M., Nandi A., Rosenblatt K.P., Goetz R., Eliseenkova A.V., Mohammadi M., Kuro-o M. (2007) BetaKlotho is required for metabolic activity of fibroblast growth factor 21. Proc Natl Acad Sci USA;104:7432-7437.
12. Suzuki M., Uehara Y., Motomura-Matsuzaka K., Oki J., Koyama Y., Kimura M., Asada M., Komi-Kuramochi A., Oka S., Imamura T. (2008) betaKlotho is required for fibroblast growth factor (FGF) 21 signaling through FGF receptor (FGFR) 1c and FGFR3c. Mol Endocrinol (Baltimore, Md);22:1006-1014.
13. Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R., Eliseenkova A.V., Mohammadi M., Rosenblatt K.P., Kliewer S.A., Kuro-o M. (2007) Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem;282:26687-26695.
14. 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. (2008) FGF-21/FGF-21 receptor interaction and activation is determined by betaKlotho. J Cell Physiol;215:1-7.
15. Holt J.A., Luo G., Billin A.N., Bisi J., McNeill Y.Y., Kozarsky K.F., Donahee M., Wang D.Y., Mansfield T.A., Kliewer S.A., Goodwin B., Jones S.A (2003) Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev;17:1581-1591.
16. Wu X., Ge H., Gupte J., Weiszmann J., Shimamoto G., Stevens J., Hawkins N. et al. (2007) Co-receptor requirements for fibroblast growth factor-19 signaling. J Biol Chem;282:29069-29072.
17. Eswarakumar V.P., Lax I., Schlessinger J. (2005) Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev;16:139-149.
18. Mohammadi M., Olsen S.K., Ibrahimi O.A. (2005) Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev;16:107-137.
19. Yie J., Hecht R., Patel J., Stevens J., Wang W., Hawkins N., Steavenson S. et al. (2009) FGF21N- and C-termini play different roles in receptor interaction and activation. FEBS Lett;583:19-24.
20. Micanovic R., Raches D.W., Dunbar J.D., Driver D.A., Bina H.A., Dickinson C.D., Kharitonenkov A. (2009) Different roles of N- and C- termini in the functional activity of FGF21. J Cell Physiol;219:227-234.
21. Olsen S.K., Ibrahimi O.A., Raucci A., Zhang F., Eliseenkova A.V., Yayon A., Basilico C., Linhardt R. J., Schlessinger J., Mohammadi M. (2004) Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity. Proc Natl Acad Sci USA;101:935-940.
22. Kiselyov V.V., Kochoyan A., Poulsen F.M., Bock E., Berezin V. (2006) Elucidation of the mechanism of the regulatory function of the Ig1 module of the fibroblast growth factor receptor 1. Protein Sci;15:2318-2322.
23. Wang F., Kan M., Yan G., Xu J., McKeehan W.L. (1995) Alternately spliced NH2-terminal immunoglobulin-like Loop I in the ectodomain of the fibroblast growth factor (FGF) receptor 1 lowers affinity for both heparin and FGF-1. J Biol Chem;270:10231-10235.
24. Rambaldi D.C., Reschiglian P., Zattoni A. (2011) Flow field-flow fractionation: recent trends in protein analysis. Anal Bioanal Chem;399:1439-1447.
25. Pollastrini J., Dillon T.M., Bondarenko P., Chou R.Y. (2011) Field flow fractionation for assessing neonatal Fc receptor and Fcgamma receptor binding to monoclonal antibodies in solution. Anal Biochem;414:88-98.
26. Tomiyama K., Maeda R., Urakawa I., Yamazaki Y., Tanaka T., Ito S. et al. (2010) Relevant use of Klotho in FGF19 subfamily signaling system in vivo. Proc Natl Acad Sci USA;107:1666-1671.
27. Plotnikov A.N., Hubbard S.R., Schlessinger J., Mohammadi M. (2000) Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell;101:413-424.
28. Plotnikov A.N., Schlessinger J., Hubbard S.R., Mohammadi M. (1999) Structural basis for FGF receptor dimerization and activation. Cell;98:641-650.
29. Ito S., Kinoshita S., Shiraishi N., Nakagawa S., Sekine S., Fujimori T., Nabeshima Y.I. (2000) Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein. Mech Dev;98:115-119.