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Sci. Signal., 17 November 2009
Vol. 2, Issue 97, p. pe75
PKM2 Tyrosine Phosphorylation and Glutamine Metabolism Signal a Different View of the Warburg Effect
Chi V. Dang*
Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
New evidence suggests that the receptor tyrosine kinase FGFR1 (fibroblast growth factor receptor 1) directly phosphorylates pyruvate kinase M2 (PKM2), resulting in reduced conversion of phosphoenolpyruvate to pyruvate, which is further catabolized to lactate by lactate dehydrogenase A. Mutation of the critical tyrosine Tyr105 to Phe rendered PKM2 more active but was associated with decreased cellular lactate production, increased oxygen consumption, and decreased hypoxic cell proliferation relative to wild-type PKM2. The apparent paradoxical effect of growth signaling through tyrosine phosphorylation, which decreases rather than increases PKM2 activity, stimulates a revised perspective of the Warburg effect. This effect, which describes the propensity for cancer cells to convert glucose to lactate at a high rate, must now accommodate links among glycolysis, the tricarboxylic acid cycle, and glutamine metabolism in cancer cells.
L. Bryan Ray (21 September 2010) Sci. Signal.3 (140), ec289.
[DOI: 10.1126/scisignal.3140ec289] |Abstract »
Guillermo Mariño and Guido Kroemer (1 June 2010) Sci. Signal.3 (124), pe19.
[DOI: 10.1126/scisignal.3124pe19] |Abstract »|Full Text »|PDF »
Nancy R. Gough (27 April 2010) Sci. Signal.3 (119), ec126.
[DOI: 10.1126/scisignal.3119ec126] |Abstract »
Paul S. Mischel and Annalisa M. VanHook (15 December 2009) Sci. Signal.2 (101), pc23.
[DOI: 10.1126/scisignal.2101pc23] |Abstract »|Full Text »|Podcast »
Taro Hitosugi, Sumin Kang, Matthew G. Vander Heiden, Tae-Wook Chung, Shannon Elf, Katherine Lythgoe, Shaozhong Dong, Sagar Lonial, Xu Wang, Georgia Z. Chen, Jianxin Xie, Ting-Lei Gu, Roberto D. Polakiewicz, Johannes L. Roesel, Titus J. Boggon, Fadlo R. Khuri, D. Gary Gilliland, Lewis C. Cantley, Jonathan Kaufman, and Jing Chen (17 November 2009) Sci. Signal.2 (97), ra73.
[DOI: 10.1126/scisignal.2000431] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth.
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|Abstract »|Full Text »|PDF »