• Purity

  >90%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to inhibit FGF acidic-dependent proliferation of NR6R‑3T3 mouse fibroblast cells. The ED    ₅₀ for this effect is 2‑6 ng/mL.

• Source

  Mouse myeloma cell line, NS0-derived

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

• Accession #

• N-terminal Sequence    
  Analysis

  Leu22

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  65 kDa (monomer)

• SDS-PAGE

  100-110 kDa, reducing conditions

Background: FGF R4

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).

• References:

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.

• Long Name:

  Fibroblast Growth Factor Receptor 4

• Entrez Gene IDs:

  2264 (Human); 14186 (Mouse)

• Alternate Names:

  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