SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor
2010 (English)In: Science Signaling, ISSN 1937-9145, Vol. 3, no 108, ra10- p.Article in journal (Refereed) Published
The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in developmental and cancer biology. Most of its biological effects have been ascribed to its tyrosine kinase activity, which propagates signaling through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. Here, we report that IGF-1 promotes the modification of IGF-1R by small ubiquitin-like modifier protein-1 (SUMO-1) and its translocation to the nucleus. Nuclear IGF-1R associated with enhancer-like elements and increased transcription in reporter assays. The SUMOylation sites of IGF-1R were identified as three evolutionarily conserved lysine residues-Lys(1025), Lys(1100), and Lys(1120)-in the beta subunit of the receptor. Mutation of these SUMO-1 sites abolished the ability of IGF-1R to translocate to the nucleus and activate transcription but did not alter its kinase-dependent signaling. Thus, we demonstrate a SUMOylation-mediated mechanism of IGF-1R signaling that has potential implications for gene regulation.
Place, publisher, year, edition, pages
2010. Vol. 3, no 108, ra10- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-130552DOI: 10.1126/scisignal.2000628ISI: 000275647700002PubMedID: 20145208OAI: oai:DiVA.org:uu-130552DiVA: diva2:349892