MISC

2004年8月

G alpha(q)/11 signaling induces apoptosis through two pathways involving reduction of Akt phosphorylation and activation of RhoA in HeLa cells

EXPERIMENTAL CELL RESEARCH
  • H Ueda
  • ,
  • R Morishita
  • ,
  • S Narumiya
  • ,
  • K Kato
  • ,
  • T Asano

298
1
開始ページ
207
終了ページ
217
記述言語
英語
掲載種別
DOI
10.1016/j.yexcr.2004.04.015
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

We have previously reported that expression of the constitutively active mutant of Galpha(11) or stimulation of m1 muscarinic acetylcholine receptor induced proteolytic activation of Rho-associated kinase (ROCK-I) by caspase and apoptosis in HeLa cells. In this study, we investigate the molecular mechanisms of Galpha(q/11)-induced apoptosis in m1 muscarinic acetylcholine receptor-expressing HeLa cells. Overexpression of Bcl-2 inhibited carbachol-induced ROCK-I cleavage, indicating a mitochondrial apoptotic pathway. Overexpression of the constitutively active mutant of Akt that delivers an anti-apoptotic survival signal had a similar influence. Insulin, a major survival factor in many cells, strongly increased phosphorylation of Akt, which was completely blocked by carbachol. This latter effect was partially inhibited by treatment with the tyrosine phosphatase inhibitors, orthovanadate and pervanadate. In parallel with these observations, carbachol attenuated insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1, an effect eliminated by orthovanadate. On the other hand, carbachol induced rapid stimulation of endogenous RhoA, and expression of a constitutively active mutant of RhoA increased ROCK-I cleavage. Orthovanadate and the dominant negative mutant of RhoA partially, and their combination completely, inhibited carbachol-induced ROCK-I cleavage and apoptosis. These results demonstrate that G(q/11) signaling induces apoptosis by reducing insulin-stimulated Akt phosphorylation through tyrosine dephosphorylation and activating RhoA in HeLa cells. (C) 2004 Elsevier Inc. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.yexcr.2004.04.015
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000222725200020&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.yexcr.2004.04.015
  • ISSN : 0014-4827
  • Web of Science ID : WOS:000222725200020

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