Fibroblast Growth Factor

Fibroblast growth factors (FGFs) are a family of structurally related polypeptide growth factors that have diverse roles in regulating cell proliferation, migration, differentiation, and apoptosis. In vertebrates, the 22 members of the FGF family range in molecular mass from 17 to 34 kDa. They share 13-71% amino acid identity. Most FGFs share an internal core region of similarity, with 28 highly conserved and six identical amino-acid residues. FGFs are highly conserved in both gene structure and amino-acid sequence between vertebrate species. Phylogenetic analysis of the human Fgf gene family can be divided into seven subfamilies: Fgf1/2, Fgf4/5/6, Fgf3/7/10/22, Fgf8/17/18, Fgf9/16/20, Fgf11/12/13/14 and Fgf19/21/23. In addition, the human and mouse FGF families do not include FGF15 or FGF19, respectively, because they are orthologs. By their mechanisms of action, FGFs also can be classified as: 1) Intracrine FGFs, FGF11-FGF14, which regulates the electrical excitability of neurons and possibly other cell types; 2) Paracrine FGFs (FGF/1/2/5, FGF3/4/6, FGF7/10/22, FGF8/17/18 and FGF9/16/20 subfamilies), act on nearby target cells as locally secreted signals via diffusion. Paracrine FGFs bindsto and activates cell surface tyrosine kinase FGFRs with heparin/heparan sulphate as a cofactor; 3) Endocrine FGFs (FGF15/19, FGF21 and FGF23) are thought to mediate their biological responses in an FGFR-dependent manner. Endocrine FGFs has low heparan sulfate-binding affinity and require αKlotho or βKlotho, which are specifically expressed in the target tissues, as a co-factor for FGFR.