Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation - PubMed (original) (raw)

Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation

J M Backer et al. EMBO J. 1992 Sep.

Abstract

IRS-1 undergoes rapid tyrosine phosphorylation during insulin stimulation and forms a stable complex containing the 85 kDa subunit (p85) of the phosphatidylinositol (PtdIns) 3'-kinase, but p85 is not tyrosyl phosphorylated. IRS-1 contains nine tyrosine phosphorylation sites in YXXM (Tyr-Xxx-Xxx-Met) motifs. Formation of the IRS-1-PtdIns 3'-kinase complex in vitro is inhibited by synthetic peptides containing phosphorylated YXXM motifs, suggesting that the binding of PtdIns 3'-kinase to IRS-1 is mediated through the SH2 (src homology-2) domains of p85. Furthermore, overexpression of IRS-1 potentiates the activation of PtdIns 3-kinase in insulin-stimulated cells, and tyrosyl phosphorylated IRS-1 or peptides containing phosphorylated YXXM motifs activate PtdIns 3'-kinase in vitro. We conclude that the binding of tyrosyl phosphorylated IRS-1 to the SH2 domains of p85 is the critical step that activates PtdIns 3'-kinase during insulin stimulation.

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References

1. 1. Nature. 1986 Sep 18-24;323(6085):226-32 - PubMed
2. 1. Nature. 1985 May 16-22;315(6016):239-42 - PubMed
3. 1. J Biol Chem. 1987 Feb 5;262(4):1842-7 - PubMed
4. 1. Nature. 1980 Jan 31;283(5746):445-53 - PubMed
5. 1. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2117-21 - PubMed

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