Literature DB >> 23728461

Signal integration by mTORC1 coordinates nutrient input with biosynthetic output.

Christian C Dibble1, Brendan D Manning.   

Abstract

Flux through metabolic pathways is inherently sensitive to the levels of specific substrates and products, but cellular metabolism is also managed by integrated control mechanisms that sense the nutrient and energy status of a cell or organism. The mechanistic target of rapamycin complex 1 (mTORC1), a protein kinase complex ubiquitous to eukaryotic cells, has emerged as a critical signalling node that links nutrient sensing to the coordinated regulation of cellular metabolism. Here, we discuss the role of mTORC1 as a conduit between cellular growth conditions and the anabolic processes that promote cell growth. The emerging network of signalling pathways through which mTORC1 integrates systemic signals (secreted growth factors) with local signals (cellular nutrients - amino acids, glucose and oxygen - and energy, ATP) is detailed. Our expanding understanding of the regulatory network upstream of mTORC1 provides molecular insights into the integrated sensing mechanisms by which diverse cellular signals converge to control cell physiology.

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Year:  2013        PMID: 23728461      PMCID: PMC3743096          DOI: 10.1038/ncb2763

Source DB:  PubMed          Journal:  Nat Cell Biol        ISSN: 1465-7392            Impact factor:   28.824


  147 in total

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2.  HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression.

Authors:  E Laughner; P Taghavi; K Chiles; P C Mahon; G L Semenza
Journal:  Mol Cell Biol       Date:  2001-06       Impact factor: 4.272

3.  Phosphorylation of Raptor by p38beta participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation.

Authors:  Xiao-Nan Wu; Xue-Kun Wang; Su-Qin Wu; Jiawei Lu; Min Zheng; Yan-Hai Wang; Huamin Zhou; Hongbing Zhang; Jiahuai Han
Journal:  J Biol Chem       Date:  2011-07-14       Impact factor: 5.157

4.  Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis.

Authors:  Tzipora Shoshani; Alexander Faerman; Igor Mett; Elena Zelin; Tamar Tenne; Svetlana Gorodin; Yana Moshel; Shlomo Elbaz; Andrei Budanov; Ayelet Chajut; Hagar Kalinski; Iris Kamer; Ada Rozen; Orna Mor; Eli Keshet; Dena Leshkowitz; Paz Einat; Rami Skaliter; Elena Feinstein
Journal:  Mol Cell Biol       Date:  2002-04       Impact factor: 4.272

5.  Mammalian TOR: a homeostatic ATP sensor.

Authors:  P B Dennis; A Jaeschke; M Saitoh; B Fowler; S C Kozma; G Thomas
Journal:  Science       Date:  2001-11-02       Impact factor: 47.728

6.  Nutrients differentially regulate multiple translation factors and their control by insulin.

Authors:  L E Campbell; X Wang; C G Proud
Journal:  Biochem J       Date:  1999-12-01       Impact factor: 3.857

7.  Glucose exerts a permissive effect on the regulation of the initiation factor 4E binding protein 4E-BP1.

Authors:  J Patel; X Wang; C G Proud
Journal:  Biochem J       Date:  2001-09-01       Impact factor: 3.857

8.  Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B.

Authors:  T Sekiguchi; E Hirose; N Nakashima; M Ii; T Nishimoto
Journal:  J Biol Chem       Date:  2000-11-09       Impact factor: 5.157

9.  TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.

Authors:  Ken Inoki; Yong Li; Tianquan Zhu; Jun Wu; Kun-Liang Guan
Journal:  Nat Cell Biol       Date:  2002-09       Impact factor: 28.824

10.  Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway.

Authors:  Brendan D Manning; Andrew R Tee; M Nicole Logsdon; John Blenis; Lewis C Cantley
Journal:  Mol Cell       Date:  2002-07       Impact factor: 17.970

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  320 in total

Review 1.  mTOR in health and in sickness.

Authors:  Dritan Liko; Michael N Hall
Journal:  J Mol Med (Berl)       Date:  2015-09-22       Impact factor: 4.599

2.  FSGS as an Adaptive Response to Growth-Induced Podocyte Stress.

Authors:  Ryuzoh Nishizono; Masao Kikuchi; Su Q Wang; Mahboob Chowdhury; Viji Nair; John Hartman; Akihiro Fukuda; Larysa Wickman; Jeffrey B Hodgin; Markus Bitzer; Abhijit Naik; Jocelyn Wiggins; Matthias Kretzler; Roger C Wiggins
Journal:  J Am Soc Nephrol       Date:  2017-07-18       Impact factor: 10.121

3.  Genetic analysis of TOR complex gene variation with human longevity: a nested case-control study of American men of Japanese ancestry.

Authors:  Brian J Morris; Timothy A Donlon; Qimei He; John S Grove; Kamal H Masaki; Ayako Elliott; D Craig Willcox; Richard Allsopp; Bradley J Willcox
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2014-03-03       Impact factor: 6.053

4.  Autophagy inhibition by biotin elicits endoplasmic reticulum stress to differentially regulate adipocyte lipid and protein synthesis.

Authors:  Senthilraja Selvam; Anand Ramaian Santhaseela; Dhasarathan Ganesan; Sudarshana Rajasekaran; Tamilselvan Jayavelu
Journal:  Cell Stress Chaperones       Date:  2019-01-15       Impact factor: 3.667

5.  Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy.

Authors:  Mark R Lundquist; Marcus D Goncalves; Ryan M Loughran; Elite Possik; Tarika Vijayaraghavan; Annan Yang; Chantal Pauli; Archna Ravi; Akanksha Verma; Zhiwei Yang; Jared L Johnson; Jenny C Y Wong; Yilun Ma; Katie Seo-Kyoung Hwang; David Weinkove; Nullin Divecha; John M Asara; Olivier Elemento; Mark A Rubin; Alec C Kimmelman; Arnim Pause; Lewis C Cantley; Brooke M Emerling
Journal:  Mol Cell       Date:  2018-05-03       Impact factor: 17.970

6.  Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome.

Authors:  Suchithra Menon; Christian C Dibble; George Talbott; Gerta Hoxhaj; Alexander J Valvezan; Hidenori Takahashi; Lewis C Cantley; Brendan D Manning
Journal:  Cell       Date:  2014-02-13       Impact factor: 41.582

Review 7.  AKT/PKB Signaling: Navigating the Network.

Authors:  Brendan D Manning; Alex Toker
Journal:  Cell       Date:  2017-04-20       Impact factor: 41.582

8.  mTOR trains heightened macrophage responses.

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Journal:  Trends Immunol       Date:  2014-12-02       Impact factor: 16.687

9.  The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1.

Authors:  Liron Bar-Peled; Lynne Chantranupong; Zhi-Yang Tsun; Roberto Zoncu; Tim Wang; Choah Kim; Eric Spooner; David M Sabatini
Journal:  Mol Cell       Date:  2013-10-03       Impact factor: 17.970

10.  Emerging role of mTOR in the response to cancer therapeutics.

Authors:  Erika Ilagan; Brendan D Manning
Journal:  Trends Cancer       Date:  2016-05
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