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Molecular Endocrinology 11 (2): 251-262
Copyright © 1997 by The Endocrine Society

The IRS-2 Gene on Murine Chromosome 8 Encodes a Unique Signaling Adapter for Insulin and Cytokine Action

Xiao Jian Sun1, Sebastian Pons, Ling-Mei Wang, Yitao Zhang, Lynne Yenush, Deborah Burks, Martin G. Myers, Jr., Erin Glasheen, Neal G. Copeland, Nancy A. Jenkins, Jacalyn H. Pierce and Morris F. White

Research Division, Joslin Diabetes Center (X.J.S., S.P., Y.Z., L.Y., D.B., M.G.M., E.G., M.F.W.) and Department of Medicine Harvard Medical School Boston, Massachusetts 02215
Laboratory of Cell and Molecular Biology (L-M.Y., J.H.P.) National Institutes of Health Bethesda, Maryland 20892
Mammalian Genetics Laboratory (N.G.C., N.A.J.) ABL-Basic Research Program National Cancer Institute-Frederick Cancer Research and Development Center Frederick, Maryland 21702

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 8 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.




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