FGFR

Supporting information

Fibroblast growth factors (FGFs) (FGF1 - 10 and 16 - 23) are mitogenic signaling molecules that have roles in angiogenesis, wound healing, cell migration, neural outgrowth and embryonic development. FGFs bind heparan sulfate glycosaminoglycans (HSGAGs), which facilitates dimerization (activation) of FGF receptors (FGFRs).

FGFRs are transmembrane catalytic receptors that have intracellular tyrosine kinase activity. There are four human genes encoding FGFRs, which produce seven different receptors (FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c and FGFR4) due to alternative splicing events occurring both in the extracellular and intracellular regions. The alternative splice isoforms are generally tissue specific: the b isoform is expressed in epithelial tissue, whereas the c isoform is expressed in mesenchymal tissue. HSGAG-FGF-FGFR binding initiates FGFR dimerization, enabling the cytoplasmic kinase domains to transphosphorylate tyrosine residues and become activated. HSGAGs also function to stabilize FGF-FGFR binding and prevent FGF degradation.

FGFs were first isolated as growth factors for fibroblasts. Since the initial discovery of FGF1 and FGF2, a further 20 structurally related FGFs have been identified, all of which are differentially expressed in many tissues. Of these 22 growth factors, 18 are FGFR ligands. FGFRs couple to the PLCγ, MAPK and PI3-K/Akt intracellular signaling cascades and there is evidence of cross talk with the Notch signaling pathway. In addition, some activated FGF-FGFR complexes are endocytosed and function directly in the cytosol and/or nucleus of the cell.

Mutations in FGFR genes are the cause of several human developmental disorders characterized by skeletal abnormalities such as achondroplasia, and upregulation of FGFR expression may lead to cell transformation and cancer.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
FGFR1 Human FGFR1 NM_023110 Q5BJG2
Mouse Fgfr1 NM_010206 P16092
Rat Fgfr1 NM_024146 O35758
FGFR2 Human FGFR2 NM_022976 Q9UQH7
Mouse Fgfr2 NM_010207 P21803
Rat Fgfr2 NM_012712 Q9R2A0
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