Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth
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Tyrosine phosphorylation of pyruvate kinase M2 gives tumor cells a metabolic advantage.
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Growth-factor-stimulated tyrosine phosphorylation of PKM2 decreases its activity.
“Moreover, growth-factor–stimulated tyrosine phosphorylation of PKM2 further decreases its activity (58, 59).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [59]
PKM2 promotes the Warburg effect and tumorigenesis.
“PKM2 promotes the Warburg effect and tumorigenesis (Christofk et al., 2008; Hitosugi et al., 2009).”
From Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1 (2011) · cites this paper as Hitosugi et al., 2009
Phosphorylation of PKM2 on Tyrosine 105 is indicative of monomer/dimer formation, prevents PKM2 tetramer configuration, and further promotes the Warburg effect.
“Phosphorylation of PKM2 on Tyrosine 105 is indicative of monomer/dimer formation, as it prevents PKM2 tetramer configuration, further promoting the Warburg effect (Hitosugi et al., 2009).”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Hitosugi et al., 2009
PKM2, when highly expressed, exists in an equilibrium of enzymatically inactive pyruvate kinase dimers (or monomers) which can translocate into the nucleus, and enzymatically active tetramers which are retained in the cytosol.
“Current data indicates that PKM2, when highly expressed, exists in an equilibrium of enzymatically inactive pyruvate kinase dimers (or monomers) which can translocate into the nucleus(Christofk et al., 2008; Hitosugi et al., 2009), and enzymatically active tetramers which are retained in the cytosol(Mazurek et al., 2005).”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Hitosugi et al., 2009
Tyrosine phosphorylation of PKM2 at residue 105 is important for the Warburg effect in hypoxia and cancer.
“This event has been shown to be important for the Warburg effect in hypoxia and cancer(Hitosugi et al., 2009).”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Hitosugi et al., 2009
Tyrosine phosphorylation of PKM2 at residue 105 inhibits the formation of a tetramer by dislodging the binding of FBP.
“Tyrosine phosphorylation of PKM2 at residue 105 will inhibit the formation of a tetramer by dislodging the binding of FBP.”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Hitosugi et al., 2009
PKM2 activity is controlled by stabilizing or destabilizing the tetramer.
“Activity is controlled by stabilizing or destabilizing the tetramer (Hitosugi et al., 2009).”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Hitosugi et al., 2009
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- Authors
- Hitosugi, T., Kang, S., Vander Heiden, M. G., Chung, T.-W., Elf, S., Lythgoe, K., Dong, S., Lonial, S., Wang, X., Chen, G. Z., Xie, J., Gu, T.-L., Polakiewicz, R. D., Roesel, J. L., Boggon, T. J., Khuri, F. R., Gilliland, D. G., Cantley, L. C., Kaufman, J., & Chen, J.
- Affiliations
- Emory University (US)
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
- Cell Signaling Technology (United States) (US)
- Novartis (Switzerland) (CH)
- Yale University (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Chen, Jing
- ORCID
- Venue
- Science Signaling
- Published
- 2009-11-17
- Volume
- 2
- Issue
- 97
- Pages
- ra73-ra73
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC2812789
- OpenAlex
- W2100260504
- Cited by
- 784
- References
- 26
- Citations by year
- 2026: 32 · 2025: 34 · 2024: 42 · 2023: 38 · 2022: 49 · 2021: 53 · 2020: 52 · 2019: 53 · 2018: 43 · 2017: 46 · 2016: 62 · 2015: 49 · 2014: 57 · 2013: 55 · 2012: 59
- FWCI
- 13.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA120272, R01CA140515, T32CA009172, CA120272)
- National Institute of General Medical Sciences (R01GM056203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- tyrosine phosphorylation, PKM2, Warburg effect, FGF receptor 1, cancer metabolism, tumor growth, fructose-1,6-bisphosphate, hypoxia, oxidative phosphorylation, lactic acid production, phosphoproteomics, cell proliferation
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Line, Fructosediphosphates, Glucose, Glycolysis, Humans, Male, Mice, Nude, Mutation, Neoplasms, Neoplasms, Experimental, Oxygen Consumption, Phosphorylation, Pyruvate Kinase, Transplantation, Heterologous, Tyrosine, Immunoblotting, K562 Cells, Proteomics, Cell Line, Tumor, Tumor Burden, Cell Proliferation, Mice, Receptor, Fibroblast Growth Factor, Type 1
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