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Mouse Anti-FGFR4 Recombinant Antibody (CBXF-0628) (CBMAB-F3176-CQ)


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Summary

Host Animal
Mouse
Specificity
Human
Clone
CBXF-0628
Antibody Isotype
IgG1, κ
Application
IHC-P, WB

Basic Information

Immunogen
Purified recombinant FGFR4 fusion protein
Specificity
Human
Antibody Isotype
IgG1, κ
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Buffer
PBS
Preservative
0.09% sodium azide
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

Target

Full Name
Fibroblast Growth Factor Receptor 4
Introduction
The protein encoded by this gene is a tyrosine kinase and cell surface receptor for fibroblast growth factors. The encoded protein is involved in the regulation of several pathways, including cell proliferation, cell differentiation, cell migration, lipid metabolism, bile acid biosynthesis, vitamin D metabolism, glucose uptake, and phosphate homeostasis. This protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment, and a cytoplasmic tyrosine kinase domain. The extracellular portion interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation.
Entrez Gene ID
2264
UniProt ID
P22455
Alternative Names
Fibroblast Growth Factor Receptor 4; EC 2.7.10.1; JTK2; TKF; Tyrosine Kinase Related To Fibroblast Growth Factor Receptor; Hydroxyaryl-Protein Kinase; Protein-Tyrosine Kinase;
Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
Biological Process
Cell migration Source: UniProtKB
Cholesterol homeostasis Source: UniProtKB
Fibroblast growth factor receptor signaling pathway Source: UniProtKB
Glucose homeostasis Source: UniProtKB
Peptidyl-tyrosine phosphorylation Source: UniProtKB
Phosphate ion homeostasis Source: UniProtKB
Positive regulation of catalytic activity Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of DNA biosynthetic process Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of gene expression Source: UniProtKB
Positive regulation of kinase activity Source: GO_Central
Positive regulation of proteolysis Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Regulation of bile acid biosynthetic process Source: UniProtKB
Regulation of extracellular matrix disassembly Source: UniProtKB
Regulation of lipid metabolic process Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Cellular Location
Endoplasmic reticulum; Endosome; Cell membrane. Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.
Isoform 2: Secreted
Isoform 3: Cytoplasm
Involvement in disease
FGFR4 variants may be involved in the pathogenesis of various cancers. Variant Arg-388 predisposes cancer patients to accelerated disease progression and may be associated with poor prognosis. It has been found in prostate cancer as well as cancers of the breast, colon, head and neck, larynx, lung, skin.
Topology
Extracellular: 22-369
Helical: 370-390
Cytoplasmic: 391-802
PTM
N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19.
Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated.
Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer.
More Infomation

Tao, Z., Cui, Y., Xu, X., & Han, T. (2022). FGFR redundancy limits the efficacy of FGFR4-selective inhibitors in hepatocellular carcinoma. Proceedings of the National Academy of Sciences, 119(40), e2208844119.

Kanzaki, H., Chiba, T., Ao, J., Koroki, K., Kanayama, K., Maruta, S., ... & Kato, N. (2021). The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma. Scientific reports, 11(1), 1-12.

Chen, T., Liu, H., Liu, Z., Li, K., Qin, R., Wang, Y., ... & Xu, Y. (2021). FGF19 and FGFR4 promotes the progression of gallbladder carcinoma in an autocrine pathway dependent on GPBAR1-cAMP-EGR1 axis. Oncogene, 40(30), 4941-4953.

Garcia-Recio, S., Thennavan, A., East, M. P., Parker, J. S., Cejalvo, J. M., Garay, J. P., ... & Perou, C. M. (2020). FGFR4 regulates tumor subtype differentiation in luminal breast cancer and metastatic disease. The Journal of clinical investigation, 130(9), 4871-4887.

Levine, K. M., Ding, K., Chen, L., & Oesterreich, S. (2020). FGFR4: A promising therapeutic target for breast cancer and other solid tumors. Pharmacology & therapeutics, 214, 107590.

Liu, Y., Cao, M., Cai, Y., Li, X., Zhao, C., & Cui, R. (2020). Dissecting the role of the FGF19-FGFR4 signaling pathway in cancer development and progression. Frontiers in cell and developmental biology, 8, 95.

Rezende Miranda, R., Fu, Y., Chen, X., Perino, J., Cao, P., Carpten, J., ... & Zhang, C. (2020). Development of a potent and specific FGFR4 inhibitor for the treatment of hepatocellular carcinoma. Journal of Medicinal Chemistry, 63(20), 11484-11497.

Raja, A., Park, I., Haq, F., & Ahn, S. M. (2019). FGF19–FGFR4 signaling in hepatocellular carcinoma. Cells, 8(6), 536.

Hatlen, M. A., Schmidt-Kittler, O., Sherwin, C. A., Rozsahegyi, E., Rubin, N., Sheets, M. P., ... & Hoeflich, K. P. (2019). Acquired On-Target Clinical Resistance Validates FGFR4 as a Driver of Hepatocellular CarcinomaAcquired Resistance to FGFR4-Targeted Therapy in HCC. Cancer Discovery, 9(12), 1686-1695.

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For research use only. Not intended for any clinical use.

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