Amino Acids Activate mTOR Complex 1 via Ca2+/CaM Signaling to hVps34
Pawan Gulati,Lawrence D. Gaspers,Stephen G. Dann,Manel Joaquin,Takahiro Nobukuni,Francois Natt,Sara C. Kozma,Andrew P. Thomas,George Thomas +8 more
TLDR
It is shown that AAs induce a rise in intracellular Ca(2+) ([Ca(2+)](i), which triggers mTOR Complex 1 and hVps34 activation, which increases the direct binding of Ca( 2+)/calmodulin (CaM) to an evolutionarily conserved motif in hVPS34 that is required for lipid kinase activity and increased mTOR complex 1 signaling.About:
This article is published in Cell Metabolism.The article was published on 2008-05-07 and is currently open access. It has received 360 citations till now. The article focuses on the topics: PI3K/AKT/mTOR pathway & Lipid kinase activity.read more
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Journal ArticleDOI
mTOR: from growth signal integration to cancer, diabetes and ageing
TL;DR: Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.
Journal ArticleDOI
mTOR regulation of autophagy
TL;DR: This review discusses the recent advances in understanding of the mechanism by which TOR regulates autophagy with focus on mammalian TOR (mTOR) and its regulation of the Autophagy machinery.
Journal Article
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. [Erratum: 2004 Sept. 23, v. 431, no. 7007, p. 485.]
Sung Hee Um,Francesca Frigerio,Mitsuhiro Watanabe,Frédéric Picard,Manel Joaquin,Melanie Sticker,Stefano Fumagalli,Peter R. Allegrini,Sara C. Kozma,Johan Auwerx +9 more
TL;DR: In this article, S6K1-deficient mice are protected against obesity owing to enhanced β-oxidation, but on a high fat diet, levels of glucose and free fatty acids still rise in S6k1-dependent mice, resulting in insulin receptor desensitization.
Journal ArticleDOI
ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase
Ryan C. Russell,Ye Tian,Hai-Xin Yuan,Hyun Woo Park,Yu Yun Chang,Joungmok Kim,Joungmok Kim,Haerin Kim,Thomas P. Neufeld,Andrew Dillin,Kun-Liang Guan +10 more
TL;DR: A molecular mechanism linking ULK to the pro-autophagic lipid kinase VPS34 is described, whereby the activated ULK1 phosphorylates Beclin-1 on Ser 14, thereby enhancing the activity of the ATG14L-containing V PS34 complexes.
Journal ArticleDOI
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
TL;DR: This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.
References
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Journal ArticleDOI
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TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.
Journal ArticleDOI
Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms
Eugenia E. Calle,Rudolf Kaaks +1 more
TL;DR: Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.
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Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase.
TL;DR: The results suggest that thapsigargin increases the concentration of cytosolic free Ca2+ in sensitive cells by an acute and highly specific arrest of the endoplasmic reticulum Ca 2+ pump, followed by a rapid Ca2+.
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
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Sung Hee Um,Francesca Frigerio,Mitsuhiro Watanabe,Frédéric Picard,Manel Joaquin,Melanie Sticker,Stefano Fumagalli,Peter R. Allegrini,Sara C. Kozma,Sara C. Kozma,Johan Auwerx,George Thomas +11 more
TL;DR: It is reported that S6K1-deficient mice are protected against obesity owing to enhanced β-oxidation, however on a high fat diet, levels of glucose and free fatty acids still rise in S6k1- deficient mice, resulting in insulin receptor desensitization.