MISC

2009年10月

Membrane Localization of Protein-Tyrosine Phosphatase 1B is Essential for its Activation of Sterol Regulatory Element-Binding Protein-1 Gene Expression and Consequent Hypertriglyceridaemia

JOURNAL OF BIOCHEMISTRY
  • Satoshi Ugi
  • ,
  • Kun Shi
  • ,
  • Yoshihiko Nishio
  • ,
  • Shinya Shimizu
  • ,
  • Baoliang Guo
  • ,
  • Osamu Sekine
  • ,
  • Kazuhiro Ikeda
  • ,
  • Katsuya Egawa
  • ,
  • Takeshi Yoshizaki
  • ,
  • Yoshio Nagai
  • ,
  • Daisuke Koya
  • ,
  • Tatsuyuki Takada
  • ,
  • Ryozo Torii
  • ,
  • Hiroshi Kimura
  • ,
  • Atsunori Kashiwagi
  • ,
  • Hiroshi Maegawa

146
4
開始ページ
541
終了ページ
547
記述言語
英語
掲載種別
DOI
10.1093/jb/mvp104
出版者・発行元
OXFORD UNIV PRESS

Protein-tyrosine phosphatase 1B (PTP1B) is a major regulator of insulin sensitivity. We have described a novel action of PTP1B in the induction of sterol regulatory element-binding protein-1 (SREBP-1) gene expression through activation of protein phosphatase 2A (PP2A). PTP1B is anchored to the endoplasmic reticulum membrane via its C-terminal tail. We have previously reported that membrane localization of PTP1B is essential for PP2A activation, which is crucial for enhancing SREBP-1 gene expression in in vitro experiments. In this study, we further investigated the physiological importance of membrane localization of PTP1B in vivo. We found that transient liver-specific overexpression of wild-type PTP1B (PTP1B-WT) using adenovirus-mediated gene transfer was associated with hypertriglyceridaemia and enhanced hepatic SREBP-1 gene expression in mice. However, overexpression of the C-terminal truncated PTP1B (PTP1B Delta CT) failed to increase hepatic SREBP-1 expression or serum triglyceride levels, despite causing insulin resistance. Our results indicate that activation of PTP1B in the liver could induce hypertriglyceridaemia and that anchoring of PTP1B to the membrane is crucial for its action.

Web of Science ® 被引用回数 : 11

リンク情報
DOI
https://doi.org/10.1093/jb/mvp104
CiNii Articles
http://ci.nii.ac.jp/naid/10026304029
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19605464
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000270709400012&DestApp=WOS_CPL

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