Gene interactions and pathways from curated databases and text-mining
J Immunol 2005, PMID: 15843586

Inhibition of mammalian target of rapamycin potentiates thrombin-induced intercellular adhesion molecule-1 expression by accelerating and stabilizing NF-kappa B activation in endothelial cells.

Minhajuddin, Mohd; Fazal, Fabeha; Bijli, Kaiser M; Amin, Md Ruhul; Rahman, Arshad

We addressed the regulatory function of mammalian target of rapamycin (mTOR) in the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. Pretreatment of HUVECs with rapamycin, an inhibitor of mTOR, augmented thrombin-induced ICAM-1 expression. Inhibition of mTOR by this approach promoted whereas over-expression of mTOR inhibited thrombin-induced transcriptional activity of NF-kappaB, an essential regulator of ICAM-1 transcription. Analysis of the NF-kappaB signaling pathway revealed that inhibition of mTOR potentiated IkappaB kinase activation resulting in a rapid and persistent phosphorylation of IkappaBalpha on Ser32 and Ser36, a requirement for IkappaBalpha degradation. Consistent with these data, we observed a more efficient and stable nuclear localization of RelA/p65 and, subsequently, the DNA binding activity of NF-kappaB by thrombin following mTOR inhibition. These data define a novel role of mTOR in down-regulating thrombin-induced ICAM-1 expression in endothelial cells by controlling a delayed and transient activation of NF-kappaB.

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Text Mining Data

NF-kappaB ⊣ mTOR: " Inhibition of mTOR by this approach promoted whereas over-expression of mTOR inhibited thrombin induced transcriptional activity of NF-kappaB , an essential regulator of ICAM-1 transcription "

ICAM-1 — NF-kappaB: " Inhibition of mTOR by this approach promoted whereas over-expression of mTOR inhibited thrombin induced transcriptional activity of NF-kappaB , an essential regulator of ICAM-1 transcription "

IkappaB kinase ⊣ mTOR: " Analysis of the NF-kappaB signaling pathway revealed that inhibition of mTOR potentiated IkappaB kinase activation resulting in a rapid and persistent phosphorylation of IkappaBalpha on Ser32 and Ser36, a requirement for IkappaBalpha degradation "

IkappaBalpha ⊣ mTOR: " Analysis of the NF-kappaB signaling pathway revealed that inhibition of mTOR potentiated IkappaB kinase activation resulting in a rapid and persistent phosphorylation of IkappaBalpha on Ser32 and Ser36, a requirement for IkappaBalpha degradation "

RelA/p65 ⊣ mTOR: " Consistent with these data, we observed a more efficient and stable nuclear localization of RelA/p65 and, subsequently, the DNA binding activity of NF-kappaB by thrombin following mTOR inhibition "

RelA/p65 ⊣ mTOR: " Consistent with these data, we observed a more efficient and stable nuclear localization of RelA/p65 and, subsequently, the DNA binding activity of NF-kappaB by thrombin following mTOR inhibition "

ICAM-1 ⊣ mTOR: " These data define a novel role of mTOR in down regulating thrombin induced ICAM-1 expression in endothelial cells by controlling a delayed and transient activation of NF-kappaB "

Manually curated Databases

No curated data.