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PMID: 23728461 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Signal integration by mTORC1 coordinates nutrient input with biosynthetic output.

Nature cell biology ·Vol. 15 ·No. 6 ·2013-06-00 ·Pages 555-64

Dibble CC, Manning BD

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.

MeSH Terms
Amino Acids/metabolism Animals Biosynthetic Pathways Energy Metabolism Food Glucose/metabolism Humans Mechanistic Target of Rapamycin Complex 1 Metabolic Networks and Pathways Multiprotein Complexes/metabolism Signal Transduction TOR Serine-Threonine Kinases/metabolism
Chemicals
Amino Acids Multiprotein Complexes Mechanistic Target of Rapamycin Complex 1 TOR Serine-Threonine Kinases Glucose
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dibble Christian C
Division of Signal Transduction, Beth Israel Deaconess Medical Center, Systems Biology Department, Harvard Medical School, Boston, Massachusetts 02115, USA.
Manning Brendan D
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2763
Published
2013-06-00
Pages
555-64
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3743096
Subset
IM
Grants
NHLBI NIH HHS · 5T32HL007893‑15 · United States
NCI NIH HHS · P01 CA120964 · United States
NHLBI NIH HHS · T32 HL007893 · United States
NCI NIH HHS · R01 CA122617 · United States
NCI NIH HHS · P01-CA120964 · United States
NCI NIH HHS · R01-CA122617 · United States
External Links
PubMed source DOI: 10.1038/ncb2763 PMC Full Text View journal details
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