title: IGF-1-dependent subunit communication of the IGF-1 holoreceptor: interactions between alpha beta heterodimeric receptor halves.
abstract: Examination of 125I-IGF-1 affinity cross-linking and beta-subunit autophosphorylation has indicated that IGF-1 induces a covalent association of isolated alpha beta heterodimeric IGF-1 receptors into an alpha 2 beta 2 heterotetrameric state, in a similar manner to that observed for the insulin receptor [Morrison, B.D., Swanson, M.L., Sweet, L.J., & Pessin, J.E. (1988) J. Biol. Chem. 263, 7806-7813]. The formation of the alpha 2 beta 2 heterotetrameric IGF-1 receptor complex from the partially purified alpha beta heterodimers was time dependent with half-maximal formation in approximately 30 min at saturating IGF-1 concentrations. The IGF-1-dependent association of the partially purified alpha beta heterodimers into an alpha 2 beta 2 heterotetrameric state was specific for the IGF-1 receptors since IGF-1 was unable to stimulate the protein kinase activity of the purified alpha beta heterodimeric insulin receptor complex. Incubation of the alpha 2 beta 2 heterotetrameric IGF-1 holoreceptor with the specific sulfhydryl agent iodoacetamide (IAN) did not alter 125I-IGF-1 binding of IGF-1 stimulation of protein kinase activity. In addition, IAN did not affect the Mn/MgATP-dependent noncovalent association of IGF-1 receptor alpha beta heterodimers into an alpha 2 beta 2 heterotetrameric state. However, IAN treatment of the alpha beta heterodimeric IGF-1 receptors inhibited the IGF-1-dependent covalent formation of the disulfide-linked alpha 2 beta 2 heterotetrameric complex. These data indicate that IGF-1 induces the covalent association of isolated alpha beta heterodimeric IGF-1 receptor complexes into a disulfide-linked alpha 2 beta 2 heterotetrameric state whereas Mn/MgATP induces a noncovalent association.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology and Biophysics, University of Iowa, Iowa City 52242.
authors.forename: P A
authors.initials: PA
authors.lastname: Wilden
authors.forename: J L
authors.initials: JL
authors.lastname: Treadway
authors.forename: B D
authors.initials: BD
authors.lastname: Morrison
authors.forename: J E
authors.initials: JE
authors.lastname: Pessin
mesh_terms: D003432:Cross-Linking Reagents / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D013002:Somatomedins; D013379:Substrate Specificity
chemical_list: D003432:Cross-Linking Reagents; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; D011972:Receptor, Insulin