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. Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily. Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 18.104.22.168; FGFR family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Cellular Component: endoplasmic reticulum; endosome; extracellular region; Golgi apparatus; integral component of plasma membrane; plasma membrane; transport vesicle
Molecular Function: ATP binding; fibroblast growth factor binding; fibroblast growth factor-activated receptor activity; heparin binding; protein binding
Biological Process: cell migration; cholesterol homeostasis; fibroblast growth factor receptor signaling pathway; glucose homeostasis; MAPK cascade; peptidyl-tyrosine phosphorylation; phosphate ion homeostasis; positive regulation of catalytic activity; positive regulation of cell proliferation; positive regulation of DNA biosynthetic process; positive regulation of ERK1 and ERK2 cascade; positive regulation of gene expression; positive regulation of protein kinase B signaling; positive regulation of proteolysis; protein autophosphorylation; regulation of bile acid biosynthetic process; regulation of extracellular matrix disassembly; regulation of lipid metabolic process