FGFR4: a tyrosine-kinase receptor 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 the MAP kinase and AKT signaling pathways. 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. Two isoforms of the human protein are formed by alternative splicing. This description may include information from UniProtKB
Protein type: EC 2.7.10.1; Protein kinase, tyrosine (receptor); Protein kinase, TK; Kinase, protein; Membrane protein, integral; TK group; FGFR family
Cellular Component: nucleoplasm; Golgi apparatus; transport vesicle; membrane; endoplasmic reticulum; integral to plasma membrane; cytoplasm; plasma membrane; integral to membrane; intercellular junction; endosome
Molecular Function: transferase activity; heparin binding; protein binding; fibroblast growth factor binding; fibroblast growth factor receptor activity; protein-tyrosine kinase activity; transferase activity, transferring phosphorus-containing groups; nucleotide binding; transmembrane receptor protein tyrosine kinase activity; kinase activity; ATP binding; protein kinase activity
Biological Process: cell migration; fibroblast growth factor receptor signaling pathway; regulation of lipid metabolic process; peptidyl-tyrosine phosphorylation; positive regulation of proteolysis; protein amino acid autophosphorylation; positive regulation of metalloenzyme activity; glucose homeostasis; protein amino acid phosphorylation; induction of an organ; positive regulation of cell proliferation; phosphate ion homeostasis; phosphorylation; lung development
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