Extracellular interactome of the FGF receptor-ligand system: complexities and the relative simplicity of the worm

Dev Dyn. 2009 Feb;238(2):277-93. doi: 10.1002/dvdy.21757.

Abstract

Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate a multitude of biological functions in embryonic development and in adult. A major question is how does one family of growth factors and their receptors control such a variety of functions? Classically, specificity was thought to be imparted by alternative splicing of the FGFRs, resulting in isoforms that bind specifically to a subset of the FGFs, and by different saccharide sequences in the heparan sulfate proteoglycan (HSPG) co-receptor. A growing number of noncanonical co-receptors such as integrins and neural cell adhesion molecule (NCAM) are now recognized as imparting additional complexity to classic FGFR signaling. This review will discuss the noncanonical FGFR ligands and speculate on the possibility that they provide additional and alternative means to determining the functional specificity of FGFR signaling. We will also discuss how invertebrate models such as C. elegans may advance our understanding of noncanonical FGFR signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing / physiology
  • Animals
  • Axons / physiology
  • Binding Sites
  • Cadherins / metabolism
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / physiology*
  • Cell Movement / physiology
  • Extracellular Space / metabolism
  • Fibroblast Growth Factors / physiology*
  • Glucuronidase / physiology
  • Heparan Sulfate Proteoglycans / metabolism
  • Klotho Proteins
  • Ligands
  • Neural Cell Adhesion Molecules / metabolism
  • Neurons / physiology
  • Protein Isoforms / physiology
  • Receptors, Fibroblast Growth Factor / physiology*
  • Signal Transduction / physiology*

Substances

  • Cadherins
  • Heparan Sulfate Proteoglycans
  • Ligands
  • Neural Cell Adhesion Molecules
  • Protein Isoforms
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • Glucuronidase
  • Klotho Proteins