The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action

Xiao Jian Sun, Sebastian Pons, Ling Mei Wang, Yitao Zhang, Lynne Yenush, Deborah Burks, Martin G. Myers, Erin Glasheen, Neal G. Copeland, Nancy A. Jenkins, Jacalyn H. Pierce, Morris F. White

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Signal transduction by insulin and IGF-1, several interleukins (IL-2, IL-4, IL-9, IL-13), interferons, GH, and other cytokines involves IRS proteins, which link the receptors for these factors to signaling molecules with Src homology-2 domains (SH2-proteins). We recently reported the amino acid sequence of murine IRS-2; in order to examine a potential genetic role for this molecule in disease, we isolated the murine IRS-2 gene and compared the expression pattern of IRS-2 against IRS-1. Like IRS-1, IRS-2 is encoded by a single exon. Whereas IRS-1 is located on murine chomosome 1, IRS-2 is located on murine chromosome S near the insulin receptor. IRS-2 is expressed together with IRS-1 in many cells and tissues; however, IRS-2 predominates in murine hematopoietic cells where it may be essential for cytokine signaling; IRS-1 predominates in adipocytes and differentiated 3T3-L1 cells where it contributes to the normal insulin response. In 32D cells, IRS-1 and IRS-2 undergo differential tyrosine phosphorylation during insulin or IL-4 stimulation, as assessed indirectly by interaction with various recombinant SH2 domains. Thus, signaling specificity through the IRS proteins may be accomplished by specific expression patterns and distinct phosphorylation patterns during interaction with various activated receptors.

Original languageEnglish (US)
Pages (from-to)251-262
Number of pages12
JournalMolecular Endocrinology
Volume11
Issue number2
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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