IGF-1-dependent subunit communication of the IGF-1 holoreceptor

Interactions between αβ heterodimeric receptor halves

Peter A. Wilden, Judith L. Treadway, Brian D. Morrison, Jeffrey E. Pessin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Examination of 125I-IGF-1 affinity cross-linking and β-subunit autophosphorylation has indicated that IGF-1 induces a covalent association of isolated αβ heterodimeric IGF-1 receptors into an α2β2 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 α2β2 heterotetrameric IGF-1 receptor complex from the partially purified αβ 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 αβ heterodimers into an α2β2 heterotetrameric state was specific for the IGF-1 receptors since IGF-1 was unable to stimulate the protein kinase activity of the purified αβ heterodimeric insulin receptor complex. Incubation of the α2β2 heterotetrameric IGF-1 holoreceptor with the specific sulfhydryl agent iodoacetamide (IAN) did not alter 125I-IGF-1 binding or IGF-1 stimulation of protein kinase activity. In addition, IAN did not affect the Mn/MgATP-dependent noncovalent association of IGF-1 receptor αβ heterodimers into an α2β2 heterotetrameric state. However, IAN treatment of the α2β2 heterodimeric IGF-1 receptors inhibited the IGF-1-dependent covalent formation of the disulfide-linked α2β2 heterotetrameric complex. These data indicate that IGF-1 induces the covalent association of isolated αβ heterodimeric IGF-1 receptor complexes into a disulfide-linked α2β2 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 αβ heterodimers into the α2β2 heterotetrameric holoreceptor complex is associated with ligand-stimulated protein kinase activation.

Original languageEnglish (US)
Pages (from-to)9734-9740
Number of pages7
JournalBiochemistry
Volume28
Issue number25
StatePublished - 1989
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor I
IGF Type 1 Receptor
Communication
Association reactions
Insulin Receptor
Protein Kinases
Disulfides
Adenosine Triphosphate
Chemical activation
Iodoacetamide
Phosphotransferases
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

IGF-1-dependent subunit communication of the IGF-1 holoreceptor : Interactions between αβ heterodimeric receptor halves. / Wilden, Peter A.; Treadway, Judith L.; Morrison, Brian D.; Pessin, Jeffrey E.

In: Biochemistry, Vol. 28, No. 25, 1989, p. 9734-9740.

Research output: Contribution to journalArticle

Wilden, Peter A. ; Treadway, Judith L. ; Morrison, Brian D. ; Pessin, Jeffrey E. / IGF-1-dependent subunit communication of the IGF-1 holoreceptor : Interactions between αβ heterodimeric receptor halves. In: Biochemistry. 1989 ; Vol. 28, No. 25. pp. 9734-9740.
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