FGFR4 : fibroblast growth factor receptor 4
Description
The FGFR4 (fibroblast growth factor receptor 4) is a protein-coding gene located on chromosome 5.
The FGFR4 gene provides instructions for making a protein called fibroblast growth factor receptor 4. This protein is part of a family of fibroblast growth factor receptors that share similar structures and functions. These receptor proteins play a role in important processes such as cell division, regulating cell growth and maturation, formation of blood vessels, wound healing, and embryo development.The FGFR4 protein interacts with specific growth factors to conduct signals from the environment outside the cell to the nucleus. The nucleus responds to these signals by switching on or off appropriate genes that help the cell adjust to changes in the environment. In response, the cell might divide, move, or mature to take on specialized functions. Although specific functions of FGFR4 remain unclear, studies indicate that the gene is involved in muscle development and the maturation of bone cells in the skull. The FGFR4 gene may also play a role in the development and maintenance of specialized cells (called foveal cones) in the light-sensitive layer (the retina) at the back of the eye.
FGFR4 is a tyrosine-protein kinase that serves as a cell-surface receptor for fibroblast growth factors. It plays a crucial role in regulating cell proliferation, differentiation, and migration. Moreover, it's involved in regulating lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism, and phosphate homeostasis. FGFR4 is essential for the normal downregulation of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. It phosphorylates PLCG1 and FRS2, initiating several signaling cascades. Activation of PLCG1 leads to the production of diacylglycerol and inositol 1,4,5-trisphosphate, key cellular signaling molecules. Phosphorylation of FRS2 triggers the recruitment of GRB2, GAB1, PIK3R1, and SOS1, mediating the activation of RAS, MAPK1/ERK2, MAPK3/ERK1, and the MAP kinase signaling pathway, as well as the AKT1 signaling pathway. FGFR4 promotes SRC-dependent phosphorylation of the matrix protease MMP14, leading to its lysosomal degradation. FGFR4 signaling is downregulated through receptor internalization and degradation, a process facilitated by MMP14. Mutations affecting FGFR4 can lead to aberrant signaling, either through constitutive kinase activation or impaired inactivation.
FGFR4 is also known as CD334, JTK2, TKF.
