title: The insulin-like growth factor-I receptor. Structure, ligand-binding mechanism and signal transduction.
abstract: 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.
authors.affiliation: Hagedorn Research Institute, Gentofte, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: De Meyts
authors.forename: B
authors.initials: B
authors.lastname: Wallach
authors.forename: C T
authors.initials: CT
authors.lastname: Christoffersen
authors.forename: B
authors.initials: B
authors.lastname: Ursø
authors.forename: K
authors.initials: K
authors.lastname: Grønskov
authors.forename: L J
authors.initials: LJ
authors.lastname: Latus
authors.forename: F
authors.initials: F
authors.lastname: Yakushiji
authors.forename: M M
authors.initials: MM
authors.lastname: Ilondo
authors.forename: R M
authors.initials: RM
authors.lastname: Shymko
mesh_terms: D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000737:chemistry* / Q000378:metabolism; D011972:Receptor, Insulin / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
chemical_list: D008024:Ligands; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins