論文

査読有り
2014年

PTP1B Inhibition Causes Rac1 Activation by Enhancing Receptor Tyrosine Kinase Signaling

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
  • Ayako Tsuchiya
  • ,
  • Takeshi Kanno
  • ,
  • Hisao Nagaya
  • ,
  • Tadashi Shimizu
  • ,
  • Akito Tanaka
  • ,
  • Tomoyuki Nishizaki

33
4
開始ページ
1097
終了ページ
1105
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1159/000358679
出版者・発行元
KARGER

Background/Aims: The present study investigated the signaling pathway underlying Rac1 activation induced by the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)cyclopropyl]-octanoic acid (DCP-LA). Methods: Activity of protein tyrosine phosphatase 1B (PTP1B) was assayed under cell-free conditions. Western blot was carried out to quantify phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt in PC-12 cells. Rac1 activity was monitored in the foerster resonance energy transfer (FRET) analysis using living and fixed PC-12 cells. Results: DCP-LA markedly suppressed PTP1B activity in a concentration (100 pM-100 mu M)-dependent manner. In the DCP-LA binding assay, fluorescein-conjugated DCPLA produced a single fluorescent signal band at 60 kDa, corresponding to the molecule of PTP1B, and the signal was attenuated or abolished by co-treatment or pretreatment with non-conjugated DCP-LA. DCP-LA significantly enhanced nerve growth factor (NGF)-stimulated phosphorylation of IRS-1 at Tyr1222 and Akt1/2 at Thr308/309 and Ser473/474 in PC-12 cells. In the FRET analysis, DCP-LA significantly enhanced NGF-stimulated Rac1 activation, which is abrogated by the phosphatidylinositol 3 kinase (PI3K) inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase-1 (PDK1) inhibitor BX912, or the Akt inhibitor MK2206. Conclusion: The results of the present study show that DCP-LA-induced PTP1B inhibition, possibly through its direct binding, causes Rac1 activation by enhancing a pathway along a receptor tyrosine kinase (RTK)/IRS-1/PI3K/Akt/Rac1 axis. Copyright (C) 2014 S. Karger AG, Basel

Web of Science ® 被引用回数 : 5

リンク情報
DOI
https://doi.org/10.1159/000358679
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24732916
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000336493100019&DestApp=WOS_CPL

エクスポート
BibTeX RIS