Recombinant Human FGFR4 Fc Chimera Protein, CF

• Reactivity: Hu
• Applications: Bioactivity
• Format: Carrier-Free

Recombinant Human FGFR4 Fc Chimera Protein, CF Summary

• Details of Functionality: Measured by its ability to inhibit FGF acidic-dependent proliferation of NR6R‑3T3 mouse fibroblast cells. The ED₅₀ for this effect is 2‑6 ng/mL.
• Source: Mouse myeloma cell line, NS0-derived human FGFR4 protein
  

  Human FGF R4 (Leu22-Asp369) Accession # P22455	IEGRMD	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #: P22455
• N-terminal Sequence: Leu22
• Structure / Form: Disulfide-linked homodimer
• Protein/Peptide Type: Recombinant Proteins
• Gene: FGFR4
• Purity: >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.01 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 65 kDa (monomer).
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 100-110 kDa, reducing conditions

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in PBS.
• Purity: >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Reconstitution Instructions: Reconstitute at 100 μg/mL in sterile PBS.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Human FGFR4 Fc Chimera Protein, CF

• CD334 antigen
• CD334
• EC 2.7.10
• EC 2.7.10.1
• FGF R4
• FGFR4
• FGFR-4
• fibroblast growth factor receptor 4
• JTK2hydroxyaryl-protein kinase
• MGC20292
• protein-tyrosine kinase
• TKF
• tyrosine kinase related to fibroblast growth factor receptor
• tyrosylprotein kinase

Background

Fibroblast growth factor receptor 4 (FGF R4), also known as CD334, is a 110 kDa glycosylated transmembrane receptor tyrosine kinase (1). Mature human FGF R4 consists of a 348 amino acid (aa) extracellular domain (ECD) with three Ig‑like domains, a 21 aa transmembrane segment, and a 412 aa cytoplasmic domain that contains the tyrosine kinase domain (2). Within the ECD, human FGF R4 shares 90% and 88% aa sequence identity with mouse and rat FGF R4, respectively. Alternate splicing generates a potentially secreted isoform with a substitution encompassing the transmembrane segment (3). A 65 kDa N‑terminally truncated isoform lacks the signal peptide and first two Ig‑like domains. This isoform is produced in human pituitary adenomas and is constitutively phosphorylated and oncogenic (4). FGF R4 is widely expressed during embryonic development and in adult liver, kidney, and lung (5‑8). It binds FGF acidic, FGF basic, FGF‑8, -15, and -19 (2, 7, 9‑12). FGF R4 associates with beta-Klotho and sulfated glycosaminoglycans, and these interactions increase the affinity of FGF R4 for its ligands as well as its signaling capacity (8, 9, 12). FGF-19 induced signaling through FGF R4 is important for the regulation of bile acid synthesis and lipid and glucose homeostasis (10, 13). FGF R4 supports glucose tolerance and insulin sensitivity and protects against hyperlipidemia (13). It is down‑regulated in the liver during fasting and is up‑regulated by insulin (10). It can exert either proliferative or apoptotic effects on hepatocytes (8, 11). FGF R4 signaling is additionally required for skeletal muscle development in limbs (7, 14). FGF R4 interacts in cis with cell surface MMP-14, leading to down‑regulation of both proteins (15). In contrast, the Arg388 variant of FGF R4, which is associated with tumor progression in human cancer, is activated and stabilized by MMP-14 (15, 16).

1. Haugsten, E.M. et al. (2010) Mol. Cancer Res. 8:1439.
2. Partanen, J. et al. (1991) EMBO J. 10:1347.
3. Takaishi, S. et al. (2000) Biochem. Biophys. Res. Commun. 267:658.
4. Ezzat, S. et al. (2002) J. Clin. Invest. 109:69.
5. Stark, K.L. et al. (1991) Development 113:641.
6. Korhonen, J. et al. (1992) Int. J. Dev. Biol. 36:323.
7. Marics, I. et al. (2002) Development 129:4559.
8. Luo, Y. et al. (2010) J. Biol. Chem. 285:30069.
9. Saxena, K. et al. (2010) J. Biol. Chem. 285:26628.
10. Shin, D.J. and T.F. Osborne (2009) J. Biol. Chem. 284:11110.
11. Wu, X. et al. (2010) J. Biol. Chem. 285:5165.
12. Nakamura, M. et al. (2011) J. Biol. Chem. 286:26418.
13. Huang, X. et al. (2007) Diabetes 56:2501.
14. Kwiatkowski, B.A. et al. (2008) J. Cell Physiol. 215:803.
15. Sugiyama, N. et al. (2010) Proc. Natl. Acad. Sci. 107:15786.
16. Bange, J. et al. (2002) Cancer Res. 62:840.

Publications for FGFR4 (685-FR)(5)

Publications using 685-FR

• C Yanucil, D Kentrup, X Li, A Grabner, K Schramm, EC Martinez, J Li, I Campos, B Czaya, K Heitman, D Westbrook, AR Wende, A Sloan, JM Roche, A Fornoni, MS Kapiloff, C Faul FGF21-FGFR4 signaling in cardiac myocytes promotes concentric cardiac hypertrophy in mouse models of diabetes Scientific Reports, 2022-05-05;12(1):7326. 2022-05-05 [PMID: 35513431] (Bioassay, Human)
• R Bartz, K Fukuchi, T Ohtsuka, T Lange, K Gruner, I Watanabe, S Hayashi, Y Oda, R Kawaida, H Komori, Y Kashimoto, P Wirtz, JA Mayer, M Redondo-Mü, S Saito, M Takahashi, H Hanzawa, E Imai, A Martinez, M Hanai, D Häussinger, RW Chapman, T Agatsuma, J Bange, R Abraham Pre-clinical development of U3-1784, a novel FGFR4 antibody against cancer, and avoidance of its on-target toxicity Mol. Cancer Ther., 2019-07-26;0(0):. 2019-07-26 [PMID: 31350344] (ELISA Capture, Human)
• A Agrawal, S Parlee, D Perez-Tilv, P Li, J Pan, PA Mroz, AM Kruse Hans, B Andersen, B Finan, A Kharitonen, RD DiMarchi Molecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity Mol Metab, 2018-05-11;13(0):45-55. 2018-05-11 [PMID: 29789271] (Bioassay, Human)
• Marklund M, Sjodal M, Beehler BC, Jessell TM, Edlund T, Gunhaga L Retinoic acid signalling specifies intermediate character in the developing telencephalon. Development, 2004-08-04;131(17):4323-32. 2004-08-04 [PMID: 15294870] (Bioassay, Chicken)
• Gunhaga L, Marklund M, Sjodal M, Hsieh JC, Jessell TM, Edlund T Specification of dorsal telencephalic character by sequential Wnt and FGF signaling. Nat. Neurosci., 2003-07-01;6(7):701-7. 2003-07-01 [PMID: 12766771] (Bioassay, Chicken)

Bioinformatics

• Gene Symbol: FGFR4
• Uniprot:
  • P22455()