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

Steven B. Waters, Keishi Yamauchi, Jeffrey E. Pessin

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

To examine the role of the insulin receptor substrate-1 (IRS-1) in mediating insulin biological responsiveness, we generated Chinese hamster ovary cell lines expressing antisense IRS-1 RNA. These cells displayed morphological alterations as well as markedly reduced growth rates compared to the parental cells. Furthermore, the antisense IRS-1 cell lines had decreased insulin-stimulated IRS-1 tyrosine phosphorylation, reduced phosphatidylinositol 3-kinase activation, and decreased thymidine incorporation relative to the parental cell line. Insulin-dependent transcriptional regulation of a serum response element/luciferase reporter construct (SRE-Luc) was also reduced in the antisense IRS-1-expressing cell lines. However, co-transfection with a plasmid directing the expression of rat IRS-1 fully restored insulin-stimulated SRE-Luc activity in the IRS-1 antisense cell lines. Thus, the inhibition in insulin signaling was a specific effect of decreased IRS-1 tyrosine phosphorylation. Taken together, these data demonstrate that insulin regulation of mitogenic signaling requires the functional expression of IRS-1 and documents its central importance in the insulin intrazellular signaling pathway.

Original languageEnglish (US)
Pages (from-to)22231-22234
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number30
StatePublished - Oct 25 1993
Externally publishedYes

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Insulin Receptor Substrate Proteins
Insulin
Cells
Cell Line
Serum Response Element
Phosphorylation
Luciferases
Tyrosine
Phosphatidylinositol 3-Kinase
Cricetulus
Thymidine
Transfection
Rats
Ovary
Plasmids
Chemical activation
RNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Functional expression of insulin receptor substrate-1 is required for insulin-stimulated mitogenic signaling. / Waters, Steven B.; Yamauchi, Keishi; Pessin, Jeffrey E.

In: Journal of Biological Chemistry, Vol. 268, No. 30, 25.10.1993, p. 22231-22234.

Research output: Contribution to journalArticle

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