Association of IRS-1 with the insulin receptor and the phosphatidylinositol 3′-kinase

Formation of binary and ternary signaling complexes in intact cells

Jonathan M. Backer, Martin G. Myers, Xiao Jian Sun, Debra J. Chin, Steven E. Shoelson, Montserrat Miralpeix, Morris F. White

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

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
Volume268
Issue number11
StatePublished - Apr 15 1993

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Phosphatidylinositol 3-Kinase
Insulin Receptor
Insulin
CHO Cells
Phosphorylation
Association reactions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Association of IRS-1 with the insulin receptor and the phosphatidylinositol 3′-kinase : Formation of binary and ternary signaling complexes in intact cells. / Backer, Jonathan M.; Myers, Martin G.; Sun, Xiao Jian; Chin, Debra J.; Shoelson, Steven E.; Miralpeix, Montserrat; White, Morris F.

In: Journal of Biological Chemistry, Vol. 268, No. 11, 15.04.1993, p. 8204-8212.

Research output: Contribution to journalArticle

Backer, Jonathan M. ; Myers, Martin G. ; Sun, Xiao Jian ; Chin, Debra J. ; Shoelson, Steven E. ; Miralpeix, Montserrat ; White, Morris F. / Association of IRS-1 with the insulin receptor and the phosphatidylinositol 3′-kinase : Formation of binary and ternary signaling complexes in intact cells. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 11. pp. 8204-8212.
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