Opposing and uncoupling effects of mTOR and S6K1 in the regulation of endothelial tissue factor expression.
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.
Ming
Xiu-Fen
XF
Division of Physiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland. xiu-fen.ming@unifr.ch
Rajapakse
Angana Gupta
AG
Carvas
João Miguel
JM
Ruffieux
Jean
J
Yang
Zhihong
Z
D000256:Adenoviridae; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
D016328:NF-kappa B; C066737:RHOA protein, human; D013925:Thromboplastin; D011494:Protein Kinases; C546842:MTOR protein, human; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein