mTORC2 regulates PGE2-mediated endothelial cell survival and migration.
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.
Transplantation Biology Center, Children's Hospital Boston, Harvard Medical School, USA.
Shirine
S
Dada
Nicolas
N
Demartines
Olivier
O
Dormond
D002465:Cell Movement; D002470:Cell Survival; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D018919:Neovascularization, Physiologic / Q000235:genetics; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D009097:Multienzyme Complexes; D046912:Multiprotein Complexes; D011506:Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020744:rac GTP-Binding Proteins; D015232:Dinoprostone