| The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. | |
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MedLine Citation:
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PMID: 21106670 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose deprivation led to a marked reduction in glutamine uptake and progressive cellular atrophy in multiple mammalian cell types. Despite the continuous presence of growth factor and an abundant supply of extracellular glutamine, interleukin-3 (IL-3)-dependent cells were unable to maintain TCA cycle metabolite pools or receptor-dependent signal transduction when deprived of glucose. This was due at least in part to down-regulation of IL-3 receptor α (IL-3Rα) surface expression in the absence of glucose. Treatment of glucose-starved cells with N-acetylglucosamine (GlcNAc) to maintain hexosamine biosynthesis restored mitochondrial metabolism and cell growth by promoting IL-3-dependent glutamine uptake and metabolism. Thus, glucose metabolism through the hexosamine biosynthetic pathway is required to sustain sufficient growth factor signaling and glutamine uptake to support cell growth and survival. |
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Authors:
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Kathryn E Wellen; Chao Lu; Anthony Mancuso; Johanna M S Lemons; Michael Ryczko; James W Dennis; Joshua D Rabinowitz; Hilary A Coller; Craig B Thompson |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-24 |
Journal Detail:
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Title: Genes & development Volume: 24 ISSN: 1549-5477 ISO Abbreviation: Genes Dev. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-16 Completed Date: 2011-02-18 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: United States |
Other Details:
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Languages: eng Pagination: 2784-99 Citation Subset: IM |
Affiliation:
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Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylglucosamine
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pharmacology Animals Atrophy Biological Transport Cell Survival Citric Acid Cycle Glucose / metabolism* Glutamine / metabolism* Hexosamines / biosynthesis* Intercellular Signaling Peptides and Proteins / pharmacology Interleukin-3 Metabolic Networks and Pathways* Mice Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Hexosamines; 0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-3; 50-99-7/Glucose; 56-85-9/Glutamine; 7512-17-6/Acetylglucosamine |
| Comments/Corrections | |
Comment In:
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Genes Dev. 2010 Dec 15;24(24):2717-22
[PMID:
21159812
]
Nat Rev Cancer. 2011 Feb;11(2):80 [PMID: 21322292 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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