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.