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Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity

Nature communications, 2015-04, Vol.6 (1), p.6780-6780, Article 6780 [Peer Reviewed Journal]

Copyright Nature Publishing Group Apr 2015 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/ncomms7780 ;PMID: 25879670

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Title:
Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity
Author: 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
Subjects: Adaptor Proteins, Vesicular Transport - metabolism ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Proliferation - genetics ; Cyclic AMP - metabolism ; Endosomal Sorting Complexes Required for Transport - genetics ; HEK293 Cells ; Humans ; Insulin Receptor Substrate Proteins - metabolism ; Insulin-Like Growth Factor I - metabolism ; Male ; Mitosis - genetics ; Nedd4 Ubiquitin Protein Ligases ; Phosphorylation ; Prostatic Neoplasms - genetics ; Rats ; Receptor, IGF Type 1 - metabolism ; Somatomedins ; Ubiquitin-Protein Ligases - genetics ; Ubiquitination ; Zebrafish ; Zebrafish Proteins - genetics
Is Part Of: Nature communications, 2015-04, Vol.6 (1), p.6780-6780, Article 6780
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/ncomms7780
PMID: 25879670
Source: Open Access: DOAJ Directory of Open Access Journals
Open Access: PubMed Central
AUTh Library subscriptions: ProQuest Central
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Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity

Copyright Nature Publishing Group Apr 2015 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/ncomms7780 ;PMID: 25879670

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