Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression

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Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression

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Title: Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression
Author: Cai, Weikang; Sakaguchi, Masaji; Kleinridders, Andre; Gonzalez-Del Pino, Gonzalo; Dreyfuss, Jonathan M.; O'Neill, Brian T.; Ramirez, Alfred K.; Pan, Hui; Winnay, Jonathon N.; Boucher, Jeremie; Eck, Michael J.; Kahn, C. Ronald

Note: Order does not necessarily reflect citation order of authors.

Citation: Cai, W., M. Sakaguchi, A. Kleinridders, G. Gonzalez-Del Pino, J. M. Dreyfuss, B. T. O'Neill, A. K. Ramirez, et al. 2017. “Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression.” Nature Communications 8 (1): 14892. doi:10.1038/ncomms14892. http://dx.doi.org/10.1038/ncomms14892.
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Abstract: Despite a high degree of homology, insulin receptor (IR) and IGF-1 receptor (IGF1R) mediate distinct cellular and physiological functions. Here, we demonstrate how domain differences between IR and IGF1R contribute to the distinct functions of these receptors using chimeric and site-mutated receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to their higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. Strikingly, replacement of leucine973 in the juxtamembrane region of IR to phenylalanine, which is present in IGF1R, mimics many of these signalling and gene expression responses. Overall, we show that the distinct activities of the closely related IR and IGF1R are mediated by their intracellular juxtamembrane region and substrate binding to this region.
Published Version: doi:10.1038/ncomms14892
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378997/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630631
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