2004
DOI: 10.1038/ng1494
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Abstract: The mammalian target of rapamycin (mTOR) has a central role in the regulation of cell growth. mTOR receives input from multiple signaling pathways, including growth factors and nutrients, to stimulate protein synthesis by phosphorylating key translation regulators such as ribosomal S6 kinase and eukaryote initiation factor 4E binding protein 1. High levels of dysregulated mTOR activity are associated with several hamartoma syndromes, including tuberous sclerosis complex, the PTEN-related hamartoma syndromes an… Show more

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Cited by 897 publications
(761 citation statements)
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“…34 At present, it is not clear whether the activation of mTOR by amino acids is direct, whether it involves the inhibition of tuberous sclerosis complex (TSC)1/2 (which inhibits mTOR), or whether the activation of mTOR occurs via decreased Ras homolog enriched in brain (Rheb) GTPase activity. 35 Recent evidence indicates that it is unlikely that the inhibition of TSC2 by amino acids is the mechanism involved. 36 The idea that mTOR is involved in the negative control of autophagy is now generally accepted, 13 but the mechanism by which this occurs is still largely unknown.…”
Section: Inhibition Of Autophagy By Amino Acidsmentioning
confidence: 99%
“…34 At present, it is not clear whether the activation of mTOR by amino acids is direct, whether it involves the inhibition of tuberous sclerosis complex (TSC)1/2 (which inhibits mTOR), or whether the activation of mTOR occurs via decreased Ras homolog enriched in brain (Rheb) GTPase activity. 35 Recent evidence indicates that it is unlikely that the inhibition of TSC2 by amino acids is the mechanism involved. 36 The idea that mTOR is involved in the negative control of autophagy is now generally accepted, 13 but the mechanism by which this occurs is still largely unknown.…”
Section: Inhibition Of Autophagy By Amino Acidsmentioning
confidence: 99%
“…In PTEN deficient mouse, the PI3K pathway is constitutively activated, which in turn activates the mammalian target of rapamycin (mTOR). The drug rapamycin inhibits mTOR kinase activity [87][88][89] .…”
Section: Disruption Of Critical Self-renewal Pathwaysmentioning
confidence: 99%
“…PTEN deficiency activates PI3K pathway, which in turn activates mTOR. Rapamycin is an active drug that inhibits mTOR kinase activity, and patients with acute leukemia respond to this drug 87,88 . In the PTEN-deficient mice, rapamycin successfully eradicated leukemia by depleting leukemiainitiating cells and rescuing the capacity of normal HSCs to provide long-term multilineage reconstitution.…”
Section: Cancer Stem Cells From a Therapeutic Perspectivementioning
confidence: 99%
“…One downstream molecule of mammalian target of rapamycin (mTOR) is ribosomal S6 kinase (p70S6K). This kinase regulates the efficiency of translation of certain mRNAs and also functions in a negative feedback loop to control Akt activity (Chiang and Abraham, 2005;Inoki et al, 2005;Martelli et al, 2007). Akt, mTOR and p70S6K activation have been associated with a more severe prognosis in breast and other cancers (Bose et al, 2002;Clark et al, 2002;DeGraffenried et al, 2004;Nagata et al, 2004;Lin et al, 2005;Tsutsui et al, 2005a, b;Klos et al, 2006;Tokunaga et al, 2006;Martelli et al, 2007).…”
Section: Introductionmentioning
confidence: 99%