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Intramolecular subunit interactions between insulin and insulin-like growth factor 1 .alpha..beta. half-receptors induced by ligand and manganese/magnesium-ATP binding

Authors :
Jeffrey E. Pessin
Anne L. Frattali
Judith L. Treadway
Source :
Biochemistry. 31:11801-11805
Publication Year :
1992
Publisher :
American Chemical Society (ACS), 1992.

Abstract

We have previously demonstrated that isolated insulin and IGF-1 alpha beta half-receptors can be reconstituted into a functional alpha 2 beta 2 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 alpha beta half-receptors. IGF-1 or Mn/MgAMPPCP binding to wild-type IGF-1 alpha beta half-receptors resulted in the specific assembly of the alpha beta half-receptors into an alpha 2 beta 2 heterotetrameric IGF-1 holoreceptor complex. Similarly, insulin binding to the kinase-deficient mutant (A/K1018) insulin alpha beta half-receptor also resulted in the specific assembly into an alpha 2 beta 2 holoreceptor complex. In contrast, Mn/MgAMPPCP treatment of A/K1018 mutant insulin alpha beta half-receptors did not induce heterotetramer assembly, consistent with the inability of this mutant receptor to bind ATP. The ability of the insulin alpha beta receptors to assemble with the IGF-1 alpha beta 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 alpha beta half-receptors were observed to assemble into an insulin/IGF-1 alpha 2 beta 2 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 alpha beta half-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Details

ISSN :
15204995 and 00062960
Volume :
31
Database :
OpenAIRE
Journal :
Biochemistry
Accession number :
edsair.doi.dedup.....47253499583b4c5b34e0c9669d37e4d8
Full Text :
https://doi.org/10.1021/bi00162a018