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Title: IGF-1-dependent subunit communication of the IGF-1 holoreceptor: Interactions between. alpha. beta. heterodimeric receptor halves

Abstract

Examination of {sup 125}I-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}{sub 2}{beta}{sub 2} heterotetrameric state, in a similar manner to that observed for the insulin receptor. The formation of the {alpha}{sub 2}{beta}{sub 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}{sub 2}{beta}{sub 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}{sub 2}{beta}{sub 2} heterotetrameric IGF-1 holoreceptor with the specific sulfhydryl agent iodoacetamide (IAN) did not alter {sup 125}I-IGF-1 binding or IGF-1 stimulation of protein kinase activity. However, IAN treatment of the {alpha}{beta} heterodimeric IGF-1 receptors inhibited the IGF-1 dependent covalent formation of the disulfide-linked {alpha}{sub 2}{beta}{sub 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}{sub 2}{beta}{sub 2} heterotetrameric state whereas Mn/MgATP induces a noncovalent association. Therefore, unlike the insulin receptor inmore » which noncovalent association is sufficient for kinase activation, only the covalent assembly of the IGF-1 receptor {alpha}{beta} heterodimers into the {alpha}{sub 2}{beta}{sub 2} heterotetrameric holoreceptor complex is associated with ligand-stimulated protein kinase activation.« less

Authors:
; ; ;  [1]
  1. Univ. of Iowa, Iowa City (USA)
Publication Date:
OSTI Identifier:
6921692
Resource Type:
Journal Article
Journal Name:
Biochemistry; (USA)
Additional Journal Information:
Journal Volume: 28:25; Journal ID: ISSN 0006-2960
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; IMMUNOGLOBULINS; CROSS-LINKING; PLACENTA; MEMBRANES; RECEPTORS; ALKYLATION; ATP; BIOCHEMICAL REACTION KINETICS; ELECTROPHORESIS; ENZYME INHIBITORS; INSULIN; IODINE 125; PHOSPHORUS 32; PHOSPHORYLATION; TIME DEPENDENCE; WOMEN; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CHEMICAL REACTIONS; DAYS LIVING RADIOISOTOPES; ELECTRON CAPTURE RADIOISOTOPES; FEMALES; FETAL MEMBRANES; GLOBULINS; HORMONES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; KINETICS; LIGHT NUCLEI; MAMMALS; MAN; MEMBRANE PROTEINS; NUCLEI; NUCLEOTIDES; ODD-EVEN NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; PEPTIDE HORMONES; PHOSPHORUS ISOTOPES; POLYMERIZATION; PRIMATES; PROTEINS; RADIOISOTOPES; REACTION KINETICS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Wilden, P A, Treadway, J L, Morrison, B D, and Pessin, J E. IGF-1-dependent subunit communication of the IGF-1 holoreceptor: Interactions between. alpha. beta. heterodimeric receptor halves. United States: N. p., 1989. Web. doi:10.1021/bi00451a029.
Wilden, P A, Treadway, J L, Morrison, B D, & Pessin, J E. IGF-1-dependent subunit communication of the IGF-1 holoreceptor: Interactions between. alpha. beta. heterodimeric receptor halves. United States. https://doi.org/10.1021/bi00451a029
Wilden, P A, Treadway, J L, Morrison, B D, and Pessin, J E. 1989. "IGF-1-dependent subunit communication of the IGF-1 holoreceptor: Interactions between. alpha. beta. heterodimeric receptor halves". United States. https://doi.org/10.1021/bi00451a029.
@article{osti_6921692,
title = {IGF-1-dependent subunit communication of the IGF-1 holoreceptor: Interactions between. alpha. beta. heterodimeric receptor halves},
author = {Wilden, P A and Treadway, J L and Morrison, B D and Pessin, J E},
abstractNote = {Examination of {sup 125}I-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}{sub 2}{beta}{sub 2} heterotetrameric state, in a similar manner to that observed for the insulin receptor. The formation of the {alpha}{sub 2}{beta}{sub 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}{sub 2}{beta}{sub 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}{sub 2}{beta}{sub 2} heterotetrameric IGF-1 holoreceptor with the specific sulfhydryl agent iodoacetamide (IAN) did not alter {sup 125}I-IGF-1 binding or IGF-1 stimulation of protein kinase activity. However, IAN treatment of the {alpha}{beta} heterodimeric IGF-1 receptors inhibited the IGF-1 dependent covalent formation of the disulfide-linked {alpha}{sub 2}{beta}{sub 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}{sub 2}{beta}{sub 2} heterotetrameric state whereas Mn/MgATP induces a noncovalent association. Therefore, unlike the insulin receptor in which noncovalent association is sufficient for kinase activation, only the covalent assembly of the IGF-1 receptor {alpha}{beta} heterodimers into the {alpha}{sub 2}{beta}{sub 2} heterotetrameric holoreceptor complex is associated with ligand-stimulated protein kinase activation.},
doi = {10.1021/bi00451a029},
url = {https://www.osti.gov/biblio/6921692}, journal = {Biochemistry; (USA)},
issn = {0006-2960},
number = ,
volume = 28:25,
place = {United States},
year = {Tue Dec 12 00:00:00 EST 1989},
month = {Tue Dec 12 00:00:00 EST 1989}
}