Introduction of Fibroblast growth factors (FGF)

Fibroblast growth factors (FGF), which was first discovered in pituitary extracts in 1973,is widely expressed in cells and tissues. The FGF family is one of the largest growth factor families, consisting of 22 members sharing 13–71% sequence similarity in mammals. FGFs possess a large range of activities in embryonic development and physiological functions in the adult. In the embryo, FGFs often signal across mesenchymal-epithelial boundaries, where they regulate organogenesis and pattern formation. The mammalian fibroblast growth factor receptor family has 4 members, FGFR1, FGFR2, FGFR3 and FGFR4. The FGFRs consist of three extracellular immunoglobulin-type domains (D1-D3), a single-span trans-membrane domain and an intracellular split tyrosine kinase domain. FGFs interact with the D2 and D3 domains, with the D3 interactions primarily responsible for ligand-binding specificity (see below). Heparan sulfate binding is mediated through the D3 domain. A short stretch of acidic amino acids located between the D1 and D2 domains has auto-inhibitory functions. This 'acid box' motif interacts with the heparan sulfate binding site to prevent receptor activation in the absence of FGFs. The signaling complex at the cell surface is believed to be a ternary complex formed between two identical FGF ligands, two identical FGFR subunits, and either one or two heparan sulfate chains.