The insulin-like growth factor-I receptor. Structure, ligand-binding mechanism and signal transduction

Horm Res. 1994;42(4-5):152-69. doi: 10.1159/000184188.


The nonclassical binding kinetics of IGF-I and insulin to their respective receptors, suggestive of negative cooperativity, can be readily explained by our recently proposed novel binding mechanism whereby the bivalent ligand bridges the two receptor alpha-subunits alternatively at opposite sites in a symmetrical receptor structure. The bivalent binding mechanism also explains bell-shaped bioactivity curves. The possible role of different binding modes versus differences in downstream signaling by insulin and IGF-I in producing specific mitogenic or metabolic responses is discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Humans
  • Kinetics
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism
  • Receptor, IGF Type 1 / chemistry*
  • Receptor, IGF Type 1 / metabolism
  • Receptor, Insulin / chemistry
  • Receptor, Insulin / metabolism
  • Signal Transduction
  • ras Proteins / metabolism


  • Ligands
  • Protein-Tyrosine Kinases
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • ras Proteins