PMID- 19914247 OWN - NLM STAT- MEDLINE DCOM- 20100121 LR - 20211203 IS - 1873-3468 (Electronic) IS - 0014-5793 (Linking) VI - 584 IP - 1 DP - 2010 Jan 4 TI - Opposing and uncoupling effects of mTOR and S6K1 in the regulation of endothelial tissue factor expression. PG - 135-40 LID - 10.1016/j.febslet.2009.11.030 [doi] AB - Rapamycin has been reported to enhance tissue factor (TF) expression. The present study investigated roles of mammalian target of rapamycin (mTOR) and its downstream S6K1 in this process. We showed here that, consistent with rapamycin, knocking-down mTOR enhanced thrombin-induced TF mRNA and protein levels, whereas silencing S6K1 mitigated up-regulation of TF protein but not TF mRNA level. The enhanced TF protein level upon mTOR-silencing was further augmented by over-expression of a constitutively active S6K1 mutant and reduced by blocking RhoA, p38(mapk) or NF-kappaB. The results reveal an opposing and uncoupling effect of mTOR and S6K1 in regulating TF expression. FAU - Ming, Xiu-Fen AU - Ming XF AD - Division of Physiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland. xiu-fen.ming@unifr.ch FAU - Rajapakse, Angana Gupta AU - Rajapakse AG FAU - Carvas, Joao Miguel AU - Carvas JM FAU - Ruffieux, Jean AU - Ruffieux J FAU - Yang, Zhihong AU - Yang Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (NF-kappa B) RN - 124671-05-2 (RHOA protein, human) RN - 9035-58-9 (Thromboplastin) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (RPS6KA1 protein, human) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Adenoviridae MH - Cells, Cultured MH - Endothelium, Vascular/*metabolism MH - Gene Knockdown Techniques MH - Humans MH - NF-kappa B/metabolism MH - Protein Kinases/genetics/*metabolism MH - RNA Interference MH - Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism MH - TOR Serine-Threonine Kinases MH - Thromboplastin/*biosynthesis/genetics MH - p38 Mitogen-Activated Protein Kinases/metabolism MH - rhoA GTP-Binding Protein EDAT- 2009/11/17 06:00 MHDA- 2010/01/22 06:00 CRDT- 2009/11/17 06:00 PHST- 2009/01/20 00:00 [received] PHST- 2009/10/05 00:00 [revised] PHST- 2009/11/09 00:00 [accepted] PHST- 2009/11/17 06:00 [entrez] PHST- 2009/11/17 06:00 [pubmed] PHST- 2010/01/22 06:00 [medline] AID - S0014-5793(09)00934-X [pii] AID - 10.1016/j.febslet.2009.11.030 [doi] PST - ppublish SO - FEBS Lett. 2010 Jan 4;584(1):135-40. doi: 10.1016/j.febslet.2009.11.030.