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Role of IRS-2 in insulin and cytokine signalling

Abstract

THE protein IRS-1 acts as an interface between signalling proteins with Src-homology-2 domains (SH2 proteins) and the receptors for insulin, IGF-1, growth hormone, several interleukins (IL-4, IL-9, IL-13) and other cytokines1–7. It regulates gene expression and stimulates mitogenesis, and appears to mediate insulin/1GF-1-stimulated glucose transport8. Thus, survival of the IRS-1 −7− mouse with only mild resistance to insulin was surprising9'10. This dilemma is provisionally resolved with our discovery of a second IRS-signalling protein. We purified and cloned a likely candidate called 4PS from myeloid progenitor cells and, because of its resemblance to IRS-1, we designate it IRS-2. Alignment of the sequences of IRS-2 and IRS-1 revealed a highly conserved amino terminus containing a pleckstrin-homology domain and a phos-photyrosine-binding domain, and a poorly conserved carboxy terminus containing several tyrosine phosphorylation motifs. IRS-2 is expressed in many cells, including tissues from IRS-1 −/− mice11, and may be essential for signalling by several receptor systems.

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Sun, X., Wang, LM., Zhang, Y. et al. Role of IRS-2 in insulin and cytokine signalling. Nature 377, 173–177 (1995). https://doi.org/10.1038/377173a0

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