2006
DOI: 10.1038/sj.onc.1209885
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Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?

Abstract: The mammalian target of rapamycin (mTOR) is a serine/ threonine kinase that controls many aspects of cellular physiology, including transcription, translation, cell size, cytoskeletal organization and autophagy. Recent advances in the mTOR signaling field have found that mTOR exists in two heteromeric complexes, mTORC1 and mTORC2. The activity of mTORC1 is regulated by the integration of many signals, including growth factors, insulin, nutrients, energy availability and cellular stressors such as hypoxia, osmo… Show more

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Cited by 348 publications
(324 citation statements)
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References 147 publications
(164 reference statements)
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“…PIP3 is produced by phosphorylation of phosphatidylinositol-4,5-bisphosphate via the phosphoinositide-3-kinase PI3K, which is activated by receptor tyrosine kinases, such as the insulin receptor. After binding to PIP3 via its PH domain, PKB is localized at the plasma membrane where it is phosphorylated, and thereby activated, by the phosphoinositide-dependent kinase PDK1, which also contains a PH domain, and by mammalian TORC2 (Fayard et al 2005;Corradetti and Guan 2006). Yeast contains two PDK1 orthologs, Pkh1 and Pkh2, which, however, contain no PH domain and are apparently activated by sphingolipids rather than by phosphoinositides (Casamayor et al 1999;Friant et al 2001;Liu et al 2005a, b).…”
Section: The Protein Kinase Sch9mentioning
confidence: 99%
“…PIP3 is produced by phosphorylation of phosphatidylinositol-4,5-bisphosphate via the phosphoinositide-3-kinase PI3K, which is activated by receptor tyrosine kinases, such as the insulin receptor. After binding to PIP3 via its PH domain, PKB is localized at the plasma membrane where it is phosphorylated, and thereby activated, by the phosphoinositide-dependent kinase PDK1, which also contains a PH domain, and by mammalian TORC2 (Fayard et al 2005;Corradetti and Guan 2006). Yeast contains two PDK1 orthologs, Pkh1 and Pkh2, which, however, contain no PH domain and are apparently activated by sphingolipids rather than by phosphoinositides (Casamayor et al 1999;Friant et al 2001;Liu et al 2005a, b).…”
Section: The Protein Kinase Sch9mentioning
confidence: 99%
“…When adenosine triphosphate (ATP) levels decrease below a threshold value, AMPK phosphorylates and activates the tuberous sclerosis complex 1/2 that inhibits the RHEB G-protein, which in turn activates the mammalian target of rapamycin (mTOR) (Inoki et al, 2003). The main function of mTOR is to regulate protein translation by direct phosphorylation of key translation regulators p70 ribosomal S6 kinase (p70-S6K) and eukaryotic initiation factor (eIF)4E-binding protein (4E-BP) (for review, see Corradetti and Guan (2006)). Recent advances in cancer research have drawn increased interest in the use of mTOR inhibitors to treat various cancers.…”
Section: Introductionmentioning
confidence: 99%
“…So far, mTOR's best-understood roles are those mediated by mTORC1, which is sensitive to the immunosuppressant drug rapamycin. mTORC1 signaling is activated by signaling via phosphatidylinositide 3-kinase and protein kinase B (PKB, also termed Akt) and by the Ras/Raf/ERK pathway (Corradetti and Guan, 2006). Because of its links to oncogenes and tumor suppressors, such as the lipid phosphatase PTEN, mTORC1 signaling is constitutively active in many tumor cells and their proliferation is inhibited by rapamycin (Easton and Houghton, 2006;Sabatini 2006).…”
Section: Introductionmentioning
confidence: 99%