Exploring mechanisms of FGF signalling through the lens of structural biology

Nat Rev Mol Cell Biol. 2013 Mar;14(3):166-80. doi: 10.1038/nrm3528. Epub 2013 Feb 13.

Abstract

Fibroblast growth factors (FGFs) mediate a broad range of functions in both the developing and adult organism. The accumulated wealth of structural information on the FGF signalling pathway has begun to unveil the underlying molecular mechanisms that modulate this system to generate a myriad of distinct biological outputs in development, tissue homeostasis and metabolism. At the ligand and receptor level, these mechanisms include alternative splicing of the ligand (FGF8 subfamily) and the receptor (FGFR1-FGFR3), ligand homodimerization (FGF9 subfamily), site-specific proteolytic cleavage of the ligand (FGF23), and interaction of the ligand and the receptor with heparan sulphate cofactor and Klotho co-receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alternative Splicing
  • Fibroblast Growth Factor 8 / genetics
  • Fibroblast Growth Factor 8 / metabolism
  • Fibroblast Growth Factor 9 / metabolism
  • Fibroblast Growth Factors / chemistry
  • Fibroblast Growth Factors / metabolism*
  • Glucuronidase / metabolism
  • Heparitin Sulfate / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Signal Transduction*

Substances

  • FGF8 protein, human
  • FGF9 protein, human
  • Fibroblast Growth Factor 9
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Heparitin Sulfate
  • FGFR1 protein, human
  • FGFR2 protein, human
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3
  • Glucuronidase
  • klotho protein