Aliases for FGFR4 Gene
External Ids for FGFR4 Gene
Previous GeneCards Identifiers for FGFR4 Gene
The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist 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 of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. The genomic organization of this gene, compared to members 1-3, encompasses 18 exons rather than 19 or 20. Although alternative splicing has been observed, there is no evidence that the C-terminal half of the IgIII domain of this protein varies between three alternate forms, as indicated for members 1-3. This particular family member preferentially binds acidic fibroblast growth factor and, although its specific function is unknown, it is overexpressed in gynecological tumor samples, suggesting a role in breast and ovarian tumorigenesis. [provided by RefSeq, Jul 2008]
GeneCards Summary for FGFR4 Gene
FGFR4 (Fibroblast Growth Factor Receptor 4) is a Protein Coding gene. Diseases associated with FGFR4 include achondroplasia and breast fibroadenoma. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include heparin binding and fibroblast growth factor binding. An important paralog of this gene is FGFR3.
UniProtKB/Swiss-Prot for FGFR4 Gene
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.
Fibroblast growth factors (FGFs) (FGF1 - 10 and 16 - 23) are mitogenic signaling molecules that have roles in angiogenesis, wound healing, cell migration, neural outgrowth and embryonic development. FGFs bind heparan sulfate glycosaminoglycans (HSGAGs), which facilitates dimerization (activation) of FGF receptors (FGFRs). FGFRs are transmembrane catalytic receptors that have intracellular tyrosine kinase activity. There are four human genes encoding FGFRs, which produce seven different receptors (FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c and FGFR4) due to alternative splicing events occurring both in the extracellular and intracellular regions. The alternative splice isoforms are generally tissue specific: the b isoform is expressed in epithelial tissue, whereas the c isoform is expressed in mesenchymal tissue. HSGAG-FGF-FGFR binding initiates FGFR dimerization, enabling the cytoplasmic kinase domains to transphosphorylate tyrosine residues and become activated. HSGAGs also function to stabilize FGF-FGFR binding and prevent FGF degradation. FGFRs couple to the PLCgamma, MAPK and PI3-K/Akt intracellular signaling cascades and there is evidence of cross talk with the Notch signaling pathway. In addition, some activated FGF-FGFR complexes are endocytosed and function directly in the cytosol and/or nucleus of the cell. Mutations in FGFR genes are the cause of several human developmental disorders characterized by skeletal abnormalities such as achondroplasia, and upregulation of FGFR expression may lead to cell transformation and cancer.