Assembly of insulin/insulin-like growth factor-1 hybrid receptors in vitro

J. L. Treadway, B. D. Morrison, I. D. Goldfine, J. E. Pessin

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Abstract

Insulin and Mn/MgATP treatment of immunoaffinity-purified αβ heterodimeric insulin receptors induced the formation of an α2β2 heterotetrameric insulin receptor complex. In contrast, insulin-like growth factor-1 (IGF-1) treatment was completely ineffective in inducing the association of αβ heterodimeric insulin receptors. Similarly, IGF-1 or Mn/MgATP, but not insulin, treatment of immunoaffinity-purified αβ heterodimeric IGF-1 receptors induced the formation of an α2β2 heterotetrameric IGF-1 receptor complex. A monoclonal antibody specific for the insulin receptor (MA5) completely immunoprecipitated all the insulin binding activity from both the α2β2 heterotetrameric and αβ heterodimeric insulin receptor complexes but did not immunoprecipitate IGF-1 receptors. Conversely, the IGF-1 receptor-specific monoclonal antibody (αIR-3) immunoprecipitated all the IGF-1 binding activity, but not insulin receptors. The simultaneous treatment of pooled equal amounts of αβ heterodimeric insulin and IGF-1 receptors with a combination of insulin and IGF-1 resulted in the formation of α2β2 heterotetrameric insulin and IGF-1 receptor complexes. However, in the mixed α2β2 heterotetrameric receptor fraction MA5 immunoprecipitated 94% of the insulin binding in addition to 27% of the IGF-1 binding activity whereas αIR-3 immunoprecipitated 97% of the IGF-1 binding in addition to 38% of the insulin binding activity. Treatment of the mixed αβ heterodimeric insulin and IGF-1 receptors with Mn/MgATP also resulted in the formation of cross-immunoreactive (42-46%) α2β2 heterotetrameric receptors. These data directly demonstrate the formation of insulin/IGF-1 hybrid receptors by both a combination of insulin plus IGF-1 or Mn/MgATP treatment of purified human placenta αβ heterodimeric insulin and IGF-1 half-receptors in vitro.

Original languageEnglish (US)
Pages (from-to)21450-21453
Number of pages4
JournalJournal of Biological Chemistry
Volume264
Issue number36
Publication statusPublished - Dec 1 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Treadway, J. L., Morrison, B. D., Goldfine, I. D., & Pessin, J. E. (1989). Assembly of insulin/insulin-like growth factor-1 hybrid receptors in vitro. Journal of Biological Chemistry, 264(36), 21450-21453.