FGF-21, a polypeptide with 210 amino acid residues produced mostly from the liver tissue. Mouse FGF- 21 shares 75% identity as human FGF-21. Recent animal studies indicate it possesses potent beneficial effects on glucose and lipid metabolism and insulin sensitivity. Increasing data shows FGF-21 can significantly stimulate glucose uptake in mature adipocytes. And the lowered LDL-cholesterol and increased HDL-cholesterol can also be observed. FGF-21 exerts its bioactivity through interaction with membrane bound FGF receptors (FGFRs) which requires β-Klotho as a co-factor to bind and activate FGFR signaling. The activation of FGF-21 can induce the stimulation of diverse downstream pathways medicated by MAPK,FRS-2, SHP-2, PI3K, raf, stat and other signaling molecules. In sum, FGF-21 induces a variety of significant beneficial metabolic changes without apparent adverse effects which makes this factor a hot candidate to treat some metabolic diseases.

Total: 207 AA. Mw: 23kDa (calculated).

N-terminal His- tag and TEV cleavage site, 25 extra AA (highlighted).

MSYYHHHHHHDYDIPTTENLYFQGAAYPIPDSSPLLQFGGQVRQRYLYTDDDQDTEAHLEIREDGTVVGAAHRSPESLLELKALKPGVIQILGVKASRFLCQQPDGALYGSPHFDPEACSFRELLLEDGYNVYQSEAHGLPLRLPQKDSPNQDATSWGPVRFLPMPGLLHEPQDQAGFLPPEPPDVGSSDPLSMVEPLQGRSPSYAS

Store lyophilized protein at –20°C. Aliquot reconstituted protein and store at –80°C.Avoid repeated freezing /thawing cycles.

Add deionized water to prepare a working stock solution of approximately 1 mg/mL and letthe lyophilized pellet dissolve completely.

BCA to determine quantity of the protein.

SDS PAGE to determine purity of the protein.

Lyophilized in 1 mg/mL in PBS.

ELISA and Western blotting.

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[2] Kharitonenkov A et al. FGF-21 as a novel metabolic regulator. J Clin Invest 115:1627–1635, 2005

[3]Alexei Kharitonenkov et al. The Metabolic State of Diabetic Monkeys Is Regulated by Fibroblast Growth Factor-21.Endocrinology .148(2):774–781. 2007

[4] Hiroshi Kurosu et al. Tissue-specific Expression of βKlotho and Fibroblast Growth Factor (FGF) Receptor Isoforms Determines Metabolic Activity of FGF19 and FGF21. J Biol Chem. 282(37): 26687–26695. 2007

[5] Ogawas Y et al.  BetaKlotho is required for metabolic activity of fibroblast growth factor 21 Proc Natl Acad Sci USA 104: 7432-7437, 2007.

[6]Steven L. PELECH et al. Fibroblast growth factor treatment of Swiss 3T3 cells activates a

subunit S6 kinase that phosphorylates a synthetic peptide substrate. Proc. Natl. Acad. Sci. USA

Vol. 83, pp. 5968-5972, August 1986

[7]Rosa Carballada et al. Phosphatidylinositol-3 kinase acts in parallel to the ERK MAP kinase in the FGF pathway during Xenopus mesoderm induction. Development 128, 35-44 (2001)

[8]Dayanand D. Deo et al. Phosphorylation of STAT-3 in Response to Basic Fibroblast Growth

Factor Occurs through a Mechanism Involving Platelet-activating Factor, JAK-2, and Src in Human Umbilical Vein Endothelial Cells. The journal of molecular chemistry. Vol. 277, No. 24, Issue of June 14, pp. 21237–21245, 2002

[9]Maria I. Kontaridis et al. Role of SHP-2 in Fibroblast Growth Factor Receptor-Mediated

Suppression of Myogenesis in C2C12 Myoblasts. Molecular and cellular biology, Vol. 22, No. 11, p. 3875–3891. 2002

[10] Dostálová I, Haluzíková D, Haluzík M.Fibroblast Growth Factor 21: A Novel Metabolic Regulator With Potential Therapeutic Properties in Obesity/Type 2 Diabetes Mellitus. Physiol. Res. 58: 1-7, 2009