Association of IRS-1 with the insulin receptor and the phosphatidylinositol 3'-kinase. Formation of binary and ternary signaling complexes in intact cells

J. M. Backer, M. G. Myers, X. J. Sun, D. J. Chin, S. E. Shoelson, M. Miralpeix, M. F. White

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132 Scopus citations


Insulin stimulates the formation of binary and ternary signaling complexes between the phosphatidylinositol (PtdIns) 3'-kinase, IRS-1, and the insulin receptor in vivo. Binary complex formation between IRS-1 and the PtdIns 3'- kinase occurs in intact cells and requires the tyrosyl phosphorylation IRS- 1, as mutant insulin receptors which weakly phosphorylate IRS-1 in vivo do not mediate formation of IRS-1/PtdIns 3'-kinase complexes in transfected CHO cells. Association with IRS-1 involves as much as 70% of total cellular PtdIns 3'-kinase activity. Insulin also stimulates the formation of ternary signaling complexes, as both IRS-1 and the PtdIns 3'-kinase are present in anti-insulin receptor immunoprecipitates from insulin-stimulated cells. Overexpression of IRS-1 in CHO cells increases the amount of PtdIns 3'- kinase activity in αIR immunoprecipitates, and IRS-1 markedly increases the in vitro binding of p85α and PtdIns 3'-kinase activity to anti-receptor immunoprecipitates. The mechanism for this association is unknown, but appears to involve the binding of IRS-1/PtdIns 3'-kinase complexes to the insulin receptor. The formation of binary and ternary complexes between the insulin receptor, IRS-1 and the PtdIns 3'-kinase may play a critical role in transmission of the insulin signal.

Original languageEnglish (US)
Pages (from-to)8204-8212
Number of pages9
JournalJournal of Biological Chemistry
Issue number11
StatePublished - Jan 1 1993


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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