Intramolecular subunit interactions between insulin and insulin-like growth factor 1 αβ half-receptors induced by ligand and Mn/MgATP binding

Judith L. Treadway, Anne L. Frattali, Jeffrey E. Pessin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We have previously demonstrated that isolated insulin and IGF-1 αβ half-receptors can be reconstituted into a functional α2β2 hybrid receptor complex [Treadway et al. (1989) J. Biol. Chem. 264, 21450-21453]. In the present study, we have examined this assembly process by determining the effect of ligand occupancy and Mn/MgATP binding on the dimerization of mutant and wild-type insulin and IGF-1 αβ half-receptors. IGF-1 or Mn/MgAMPPCP binding to wild-type IGF-1 αβ half-receptors resulted in the specific assembly of the αβ half-receptors into an α2β2 heterotetrameric IGF-1 holoreceptor complex. Similarly, insulin binding to the kinase-deficient mutant (A/K1018) insulin αβ half-receptor also resulted in the specific assembly into an α2β2 holoreceptor complex. In contrast, Mn/MgAMPPCP treatment of A/K1018 mutant insulin αβ half-receptors did not induce heterotetramer assembly, consistent with the inability of this mutant receptor to bind ATP. The ability of the insulin αβ receptors to assemble with the IGF-1 αβ half-receptors was used to examine the intermolecular subunit interactions responsible for dimerization. In the presence of Mn/MgAMPPCP, the wild-type insulin and wild-type IGF-1 αβ half-receptors were observed to assemble into an insulin/IGF-1 α2β2 hybrid receptor complex. Similarly, a combination of insulin and IGF-1 induced hybrid receptor formation between wild-type IGF-1 and A/K1018 mutant insulin αβ half-receptors. In contrast, mixing insulin-occupied A/K1018 mutant insulin αβ half-receptors with Mn/MgAMPPCP-occupied wild-type IGF-1 αβ half-receptors did not result in hybrid receptor formation. Thus, these data demonstrate that ligand binding to the α subunit and Mn/MgATP binding to the β subunit do not result in complementary conformational changes necessary for αβ half-receptor dimerization.

Original languageEnglish (US)
Pages (from-to)11801-11805
Number of pages5
JournalBiochemistry
Volume31
Issue number47
StatePublished - 1992
Externally publishedYes

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Somatomedins
IGF Type 1 Receptor
Insulin-Like Growth Factor I
Insulin Receptor
Adenosine Triphosphate
Insulin
Ligands
Dimerization
Phosphotransferases

ASJC Scopus subject areas

  • Biochemistry

Cite this

Intramolecular subunit interactions between insulin and insulin-like growth factor 1 αβ half-receptors induced by ligand and Mn/MgATP binding. / Treadway, Judith L.; Frattali, Anne L.; Pessin, Jeffrey E.

In: Biochemistry, Vol. 31, No. 47, 1992, p. 11801-11805.

Research output: Contribution to journalArticle

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