Abstract: This chapter gives an introduction on the fibroblast growth factor (FGF) family constituting a large family of approximately 20 structurally related growth factors. FGFs 1-10 function as paracrine factors and bind FGF receptors (FGFRs), but the intracellular FGFs 11-14 do not bind FGFRs possessing different functions. Members of the FGF family are structurally similar, with approximately 14% sequence homology and a core region containing conserved amino acid sequences and structural motifs. The core structure represents the 18-kilodalton (kDa) FGF2. FGF requires heparan sulphate to activate the receptors. The growth factors bind heparan sulphate polysaccharides, and this complex facilitates binding to and activation of FGFR. Many molecular features of the polysaccharides enter into the interaction with growth factors. The systemic effects exerted by some FGFs require the transmembrane protein klotho or β-klotho, besides the conventional FGFRs for their function. FGF23 binds FGFR, and klotho is believed to facilitate this process by functioning as a co-receptor. The crystal structure of the complex between FGF1 and FGF2 with the ligand-binding domains D2 and D3 of FGFR1 and FGFR2 has revealed that the interfaces between FGF-D2 and FGF-linker determine the specificity of interaction between FGF and FGFR. FGF targets a variety of cell types and regulate an array of biological processes such as cell differentiation, motility, proliferation, apoptosis, angiogenesis in wound healing, regulation of metabolism, and several pathological conditions.
Publication Year: 2011
Publication Date: 2011-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 1
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