The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
In vivo regulation of monomer-tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1,6-bisphosphate
Open accessAbstract
The activity of pyruvate kinase, subtype M2 (PKM2), is known to be increased by fructose 1,6-bisphosphate (Fru-1,6-P2), one of the metabolites in the glycolytic pathway. Recently, we have shown that in vitro, Fru-1,6-P2 activated the association of monomer to form the tetrameric PKM2. To ascertain whether this mode of regulation also occurs in vivo, we prepared monomer-specific monoclonal antibody and quantified the monomer formation in situ in cultured cells by immunocytochemistry. The intracellular Fru-1,6-P2 was manipulated by the glucose concentration in the media. At the physiological concentration of glucose (4-6 mM), 30-35% of PK existed as a monomer. However, PKM2 was dissociated into monomer within minutes after cells were deprived of glucose. The maximal level of monomer was detected after 1 h at 37 degrees C. Monomer was rapidly (within minutes) converted to tetramer after addition of glucose. Furthermore, when cells cultured in 10 mM of glucose were treated with cytochalasin B, an inhibitor of the glucose transporter, a maximal level of monomer was detected within 20-30 min. Determination of Fru-1,6-P2 indicated that its intracellular concentration decreased concomitantly with the reduction in glucose concentration in the medium. These results indicate that monomer-tetramer inter-conversion is a major in vivo cellular regulatory mechanism in response to changes in the extracellular glucose concentration via Fru-1,6-P2.
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“The pyruvate kinase activity of the tetramers can be regulated by the concentration of the naturally occurring upstream glycolytic intermediate FBP (Ashizawa et al., 1991; Jurica et al., 1998), serine (Chaneton et al., 2012), as well as by a multitude of post-translational modifications (Wu and Le, 2013) including tyrosine phosphorylation.”
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 Ashizawa et al., 1991
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“Tyrosine phosphorylation of PKM2 at residue 105 will inhibit the formation of a tetramer by dislodging the binding of FBP.”
InfluentialRegulation of pyruvate metabolism and human disease
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Metadata
- Authors
- Ashizawa, K., Willingham, M. C., Liang, C. M., & Cheng, S. Y.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1991-09
- Volume
- 266
- Issue
- 25
- Pages
- 16842-16846
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1484073306
- Cited by
- 172
- References
- 12
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 16 · 2020: 5 · 2019: 13 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 6 · 2014: 8 · 2013: 14 · 2012: 16
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- PKM2, fructose-1,6-bisphosphate, glucose regulation, glucose deprivation, cytochalasin B, glucose transporter inhibition, enzyme oligomerization, glycolysis, monoclonal antibodies
- MeSH terms
- Thyroid Hormone-Binding Proteins, Animals, Antibodies, Monoclonal, Carrier Proteins, Cell Line, Cytochalasin B, Fluorescent Antibody Technique, Fructosediphosphates, Glucose, Humans, Kinetics, Membrane Proteins, Precipitin Tests, Pyruvate Kinase, Thyroid Hormones, Triiodothyronine, Macromolecular Substances
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