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Sci. Signal., 9 February 2010
Vol. 3, Issue 108, p. ra10
[DOI: 10.1126/scisignal.2000628]

RESEARCH ARTICLES

Editor's Summary

Alternative Pathway
Insulin-like growth factor 1 receptor (IGF-1R) is a receptor tyrosine kinase (RTK) that mediates the effects of the protein hormone IGF-1. Binding of IGF-1 to IGF-1R leads to the transphosphorylation of tyrosine residues in the β subunits of the receptor and the activation of its tyrosine kinase activity. Activated IGF-1R stimulates the phosphatidylinositol 3-kinase (PI3K)–Akt and mitogen-activated protein kinase (MAPK) signaling pathways, which promote cell growth and proliferation. Noting that the activities of IGF-1R and other RTKs are modulated by posttranslational modifications, such as ubiquitination, Sehat et al. investigated a role for small ubiquitin-like modifier (SUMO) protein in the regulation of IGF-1R signaling. IGF-1 stimulated the SUMOylation of IGF-1R at three lysine residues in the β subunit of the receptor, which led to its nuclear translocation. Mutation of these residues blocked SUMOylation of the receptor and prevented its accumulation in the nucleus but did not interfere with endocytosis of the receptor or its activation of the PI3K or MAPK pathways. Nuclear IGF-1R bound to putative enhancer sites in genomic DNA and drove transcription of target genes in reporter assays. Together, these findings present an alternative mechanism of signaling by the IGF-1R that may have implications for gene expression.

Citation: B. Sehat, A. Tofigh, Y. Lin, E. Trocmé, U. Liljedahl, J. Lagergren, O. Larsson, SUMOylation Mediates the Nuclear Translocation and Signaling of the IGF-1 Receptor. Sci. Signal. 3, ra10 (2010).

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