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Functional expression of insulin receptor substrate-1 is required for insulin-stimulated mitogenic signaling

S B Waters1, K Yamauchi, J E Pessin

  • 1Department of Physiology and Biophysics, University of Iowa, Iowa City 52242.

The Journal of Biological Chemistry
|October 25, 1993
PubMed

Insights

Insulin receptor substrate-1 (IRS-1) is crucial for insulin signaling. Reduced IRS-1 levels impair cell growth and insulin

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Insulin receptor substrate-1 (IRS-1) is a key mediator of insulin signaling.
  • Understanding IRS-1's role is vital for comprehending insulin's biological effects.

Purpose of the Study:

  • To investigate the role of IRS-1 in mediating insulin's biological responsiveness.
  • To elucidate the impact of reduced IRS-1 expression on insulin signaling pathways.

Main Methods:

  • Generated Chinese hamster ovary (CHO) cell lines expressing antisense IRS-1 RNA.
  • Assessed cell morphology, growth rates, and insulin-stimulated signaling pathways.
  • Measured IRS-1 tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3K) activation, and thymidine incorporation.

Main Results:

  • Antisense IRS-1 CHO cells showed altered morphology and reduced growth rates.
  • Decreased insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activation were observed.
  • Insulin-dependent transcriptional regulation via SRE-Luc was significantly reduced.

Conclusions:

  • Functional expression of IRS-1 is essential for insulin-regulated mitogenic signaling.
  • IRS-1 plays a central role in the intracellular insulin signaling pathway.
  • Reduced IRS-1 specifically inhibits insulin-induced signaling events.

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