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タイトル: Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity
著者: Fukushima, Toshiaki
Yoshihara, Hidehito
Furuta, Haruka
Kamei, Hiroyasu
Hakuno, Fumihiko
Luan, Jing
Duan, Cunming
Saeki, Yasushi
Tanaka, Keiji
Iemura, Shun-Ichiro
Natsume, Tohru
Chida, Kazuhiro
Nakatsu, Yusuke
Kamata, Hideaki
Asano, Tomoichiro
Takahashi, Shin-Ichiro
キーワード: Biological sciences
Cell biology
発行日: 2015年4月15日
出版者: Nature Publishing Group
掲載誌情報: Nature Communications Online Edition: 2015/4/16 (Japan time), doi:10.1038/ncomms7780.
関連URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/novel-regulatory-mechanisms-of-animal-growth-and-cell-proliferation.html
http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/novel-regulatory-mechanisms-of-animal-growth-and-cell-proliferation.html
http://www.nature.com/ncomms/2015/150416/ncomms7780/abs/ncomms7780.html
抄録: Insulin-like growth factors (IGFs) induce proliferation of various cell types and play important roles in somatic growth and cancer development. Phosphorylation of insulin receptor substrate (IRS)-1/2 by IGF-I receptor tyrosine kinase is essential for IGF action. Here we identify Nedd4 as an IRS-2 ubiquitin ligase. Nedd4 monoubiquitinates IRS-2, which promotes its association with Epsin1, a ubiquitin-binding protein. Nedd4 recruits IRS-2 to the membrane, probably through promoting Epsin1 binding, and enhances IGF-I receptor-induced IRS-2 tyrosine phosphorylation. In thyroid FRTL-5 cells, activation of the cyclic AMP pathway increases the association of Nedd4 with IRS-2, thereby enhancing IRS-2-mediated signalling and cell proliferation induced by IGF-I. The Nedd4 and IRS-2 association is also required for maximal activation of IGF-I signalling and cell proliferation in prostate cancer PC-3 cells. Nedd4 overexpression accelerates zebrafish embryonic growth through IRS-2 in vivo. We conclude that Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity.
内容記述: UTokyo Research掲載「動物の成長や細胞の増殖の新しい調節機構を発見」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/novel-regulatory-mechanisms-of-animal-growth-and-cell-proliferation.html
UTokyo Research "Novel regulatory mechanisms of animal growth and cell proliferation" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/novel-regulatory-mechanisms-of-animal-growth-and-cell-proliferation.html
URI: http://hdl.handle.net/2261/58609
ISSN: 2041-1723 (online)
出現カテゴリ:014 自然科学
1162210 学術雑誌論文

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