Journal ArticleDOI
Tor signalling in bugs, brain and brawn.
Estela Jacinto,Michael N. Hall +1 more
TLDR
Findings indicate that TOR also controls the growth of non-proliferating cells, such as neurons and muscle cells, and by associating with regulatory proteins and inhibiting phosphatases, controls the activity of multiphosphorylated effectors.Abstract:
TOR--a highly conserved atypical protein kinase and the 'target of rapamycin', an immunosuppressant and anti-cancer drug--controls cell growth TOR controls the growth of proliferating yeast, fly and mammalian cells in response to nutrients Recent findings, however, indicate that TOR also controls the growth of non-proliferating cells, such as neurons and muscle cells Furthermore, TOR, by associating with regulatory proteins and inhibiting phosphatases, controls the activity of multiphosphorylated effectorsread more
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Upstream and downstream of mTOR
Nissim Hay,Nahum Sonenberg +1 more
TL;DR: Both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis are described.
Journal ArticleDOI
Molecular mechanisms of mTOR-mediated translational control
Xiaoju Max Ma,John Blenis +1 more
TL;DR: Recent findings on the regulators and effectors of mTOR are highlighted and specific cases that serve as paradigms for the different modes of m TOR regulation and its control of translation are discussed.
Journal ArticleDOI
Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.
Maximiliano G. Gutierrez,Sharon Master,Sudha Singh,Gregory A. Taylor,María Isabel Colombo,Vojo Deretic +5 more
TL;DR: It is demonstrated that autophagic pathways can overcome the trafficking block imposed by M. tuberculosis, which is a hormonally, developmentally, and immunologically regulated process, represents an underapp appreciated innate defense mechanism for control of intracellular pathogens.
Journal ArticleDOI
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
Estela Jacinto,Robbie Loewith,Anja Schmidt,Shuo Lin,Markus A. Rüegg,Alan Hall,Michael N. Hall +6 more
TL;DR: Two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.
Journal ArticleDOI
SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity
Estela Jacinto,Valeria Facchinetti,Dou Liu,Nelyn Soto,Shiniu Wei,Sung Yun Jung,Qiaojia Huang,Jun Qin,Bing Su +8 more
TL;DR: It is reported that SIN1/MIP1 is an essential TORC2/PDK2 subunit for Akt/PKB Ser473 phosphorylation in the hydrophobic motif and that the Sin1-rictor-mTOR function in Akt-Ser473 phosphories is required forTORC2 function in cell survival but is dispensable for TORC1 function.
References
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Journal ArticleDOI
Oncogenic kinase signalling
Peter Blume-Jensen,Tony Hunter +1 more
TL;DR: How oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity is emphasized and an update is provided on the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
Journal ArticleDOI
The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses
TL;DR: This book aims to investigate elementary forms of learning and memory at a cellular molecular level—as specific molecular activities within identified nerve cells withinidentified nerve cells.
Journal ArticleDOI
mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery
Do Hyung Kim,Dos D. Sarbassov,Siraj M. Ali,Jessie E. King,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is reported that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.
Journal ArticleDOI
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
Journal ArticleDOI
Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.
Sue C. Bodine,Trevor Stitt,Michael Gonzalez,William O. Kline,Gretchen L. Stover,Roy Bauerlein,Elizabeth Zlotchenko,Angus Scrimgeour,John C. Lawrence,David J. Glass,George D. Yancopoulos +10 more
TL;DR: It is concluded that the activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of this pathway can oppose muscle atrophy induced by disuse.