FGFR

Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinase members expressed on the cell membrane that are involved in a variety of biological processes, including cell growth, migration, differentiation, survival, and apoptosis, and are essential for embryonic and neural development, skeletal and organ formation, and adult tissue homoeostasis. As their name implies, FGFRs bind to members of the fibroblast growth factor family of proteins, mediating signal transduction. FGFRs are made of N-terminal extracellular domains with three different immunoglobulin-like subdomains (D1, D2 and D3), a transmembrane domain and a cytoplasmic tyrosine kinase domain. In humans, six FGFR family members are currently identified (FGFR1-6). Among them, FGFR5 (also known as “FGFRL1”) is a truncated FGFR without intracellular kinase domain and plays a role in regulating excessive activation of the FGF-FGFR1 signaling pathway. Binding of ligand triggers functional dimerization and transphosphorylation of FGFRs, activation of four key downstream signalling pathways: RAS-RAF-MAPK, PI3K-AKT, STAT and PLCγ. FGF/FGFR signaling participates in the development of almost all organs such as lung, heart, urinary system, brain, skeleton, muscle, and skin/appendage, as well as angiogenesis and lymphangiogenesis. The malfunction of FGF/FGFR signaling axis is observed in a variety of human diseases, such as congenital craniosynostosis and dwarfism syndromes, as well as chronic kidney disease (CKD), obesity, insulin resistance, and various tumors.