胰岛素样生长因子-1受体（IGF-IR）是一种在质膜中发现的受体酪氨酸激酶，它会介导IGF-1（这是一种参与促进细胞生长和增殖的蛋白质激素）的作用。异常的IGF-1R信号传导与多种癌症有关。
在2010年2月9日刊的Science Signaling的一篇Research Article中，Sehat 等人研究显示，IGF-1可刺激一种叫作SUMOylation的IGF-1R的修饰，这种修饰可使该受体能够被转运到细胞核，并在那里与特别的DNA序列结合以增进标靶基因的表达。IGF-1R的这些核效应不同于其在质膜上的信号传导，它可能与IGF-1在癌症中的作用有关。（生物谷Bioon.com）
生物谷推荐原始出处：
Sci. Signal., 9 February 2010 DOI: 10.1126/scisignal.2000628
SUMOylation Mediates the Nuclear Translocation and Signaling of the IGF-1 Receptor
Bita Sehat1, Ali Tofigh2*, Yingbo Lin1*, Eric Trocmé1, Ulrika Liljedahl3, Jens Lagergren2, and Olle Larsson1
1 Department of Oncology and Pathology, Karolinska Institutet, Cancer Center Karolinska, R8:04, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
2 KTH Royal Institute of Technology, Computational Biology, Stockholm Bioinformatics Centre, SE-100 44 Stockholm, Sweden.
3 Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
Abstract: 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—Lys1025, Lys1100, and Lys1120—in the β 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.
