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 # P22455IEGRMD Human IgG1
(Pro100-Lys330)N-terminus C-terminus Accession #
N-terminal Sequence
AnalysisLeu22
Structure / Form
Disulfide-linked homodimer
Predicted Molecular Mass
65 kDa (monomer)
SDS-PAGE
100-110 kDa, reducing conditions
685-FR |
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Formulation Lyophilized from a 0.2 μm filtered solution in PBS. | ||
Reconstitution Reconstitute at 100 μg/mL in sterile PBS. | ||
Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below. | ||
Stability & Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
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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:
Haugsten, E.M. et al. (2010) Mol. Cancer Res. 8:1439.
Partanen, J. et al. (1991) EMBO J. 10:1347.
Takaishi, S. et al. (2000) Biochem. Biophys. Res. Commun. 267:658.
Ezzat, S. et al. (2002) J. Clin. Invest. 109:69.
Stark, K.L. et al. (1991) Development 113:641.
Korhonen, J. et al. (1992) Int. J. Dev. Biol. 36:323.
Marics, I. et al. (2002) Development 129:4559.
Luo, Y. et al. (2010) J. Biol. Chem. 285:30069.
Saxena, K. et al. (2010) J. Biol. Chem. 285:26628.
Shin, D.J. and T.F. Osborne (2009) J. Biol. Chem. 284:11110.
Wu, X. et al. (2010) J. Biol. Chem. 285:5165.
Nakamura, M. et al. (2011) J. Biol. Chem. 286:26418.
Huang, X. et al. (2007) Diabetes 56:2501.
Kwiatkowski, B.A. et al. (2008) J. Cell Physiol. 215:803.
Sugiyama, N. et al. (2010) Proc. Natl. Acad. Sci. 107:15786.
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
