mTORC2 regulates PGE2-mediated endothelial cell survival and migration.

Details

Serval ID
serval:BIB_560ED2F49720
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
mTORC2 regulates PGE2-mediated endothelial cell survival and migration.
Journal
Biochemical and Biophysical Research Communications
Author(s)
Dada S., Demartines N., Dormond O.
ISSN
1090-2104[electronic], 0006-291X[linking]
Publication state
Published
Issued date
2008
Volume
372
Number
4
Pages
875-879
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Prostaglandin E(2) (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE(2)-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE(2)-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE(2)-mediated endothelial cell responses.
Keywords
Cell Movement, Cell Survival, Dinoprostone/metabolism, Dinoprostone/pharmacology, Endothelial Cells/drug effects, Endothelial Cells/metabolism, Humans, Multienzyme Complexes/antagonists & inhibitors, Multienzyme Complexes/genetics, Neovascularization, Physiologic/genetics, Proto-Oncogene Proteins c-akt/metabolism, RNA, Small Interfering/genetics, Transcription Factors/antagonists & inhibitors, Transcription Factors/genetics, rac GTP-Binding Proteins/metabolism
Pubmed
Web of science
Create date
17/02/2010 10:18
Last modification date
20/08/2019 14:10
Usage data