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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Citations
Cites
(1974) · Elsevier eBooks · doi:10.1016/b978-0-12-091304-6.x5001-0 · Cited by 6,786
HORMONAL REGULATION OF MAMMALIAN GLUCOSE TRANSPORT
Simpson, I. A., & Cushman, S. W. (1986) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.55.070186.005211 · Cited by 398
[25] Pyruvate kinase isozymes from rat
Imamura, K., & Tanaka, T. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(82)90121-5 · Cited by 142
Ashizawa, K., McPhie, P., Lin, K., & Cheng, S. Y. (1991) · Biochemistry · doi:10.1021/bi00243a010 · Cited by 101
Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase.
Kato, H., Fukuda, T., Parkison, C., McPhie, P., & Cheng, S.-Y. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.20.7861 · Cited by 99
Lin, K., Fukuda, T., & Cheng, S.-Y. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)34100-6 · Cited by 56
HASUMURA, S., Kitagawa, S., Lovelace, E., Willingham, M. C., Pastan, I. H., & Cheng, S.-Y. (1986) · Biochemistry · doi:10.1021/bi00372a014 · Cited by 41
Kitagawa, S., Obata, T., HASUMURA, S., Pastan, I. H., & Cheng, S.-Y. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61442-5 · Cited by 35
A cytoplasmic thyroid hormone binding protein: characterization using monoclonal antibodies
Obata, T., Fukuda, T., Willingham, M. C., Liang, C., & Cheng, S. Y. (1989) · Biochemistry · doi:10.1021/bi00428a030 · Cited by 15
Regulation of thyroid hormone binding to its cytosolic binding protein by L-α-alanine
Ashizawa, K., Kato, H., McPhie, P., & Cheng, S.-Y. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)92065-8 · Cited by 10
Research works printed but not linked: 2
- Richert, 1982, J. Clin. Virol., 62, 385
- Eigenbrodt, 1985, 2, 142
Cited by
Sorted by citations
Items 101–172 of 172
Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension
Plecitá‐Hlavatá, L., D’Alessandro, A., Kasmi, K. E., Li, M., Zhang, H., Ježek, P., & Stenmark, K. R. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-63245-2_14 · Cited by 26
Li, Y., Chang, Y., Zhang, L., Feng, Q.-P., Liu, Z., Zhang, Y., Zuo, J., Meng, Y., & Fang, F. (2005) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-5535-1 · Cited by 25
Mitotic Chromosomal Bcl-2: II. Localization to Interphase Nuclei
Schandl, C. A., Li, S., Re, G. G., Fan, W., & Willingham, M. C. (1999) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549904700204 · Cited by 24
The Xenopus oocyte: A model for studying the metabolic regulation of cancer cell death
Nutt, L. K. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.03.015 · Cited by 24
Collins, R. A., McNally, T., Fothergill‐Gilmore, L. A., & Muirhead, H. (1995) · Biochemical Journal · doi:10.1042/bj3100117 · Cited by 23
Double role of pyruvate kinase type M2 in the regulation of phosphometabolite pools
EIGENBRODT, E., Mazurek, S., & Friis, R. R. (1998) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8950-6_2 · Cited by 22
A novel mutation ofPANK4causes autosomal dominant congenital posterior cataract
Sun, M., Chen, C., Hou, S., Li, X., Wang, H., Zhou, J., Chen, X., Liu, P., Kijlstra, A., Lin, S., et al. (2018) · Human Mutation · doi:10.1002/humu.23696 · Cited by 21
Upadhyay, S., Bhardwaj, M., Kumar, S. P., Khan, S., Kumar, A., & Hassan, M. I. (2025) · Biochemistry · doi:10.1021/acs.biochem.5c00009 · Cited by 20
Metabolic Alterations During the Growth of Tumour Spheroids
Bloch, K. M., Smith, H., Parsons, V. V. H., Gavaghan, D. J., Kelly, M., Fletcher, A. G., Maini, P. K., & Callaghan, R. (2013) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-013-9757-7 · Cited by 22
Power to see—Drivers of aerobic glycolysis in the mammalian retina: A review
Haydinger, C. D., Kittipassorn, T., & Peet, D. J. (2020) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.13833 · Cited by 21
Phosphorylation of pyruvate kinase type K is restricted to the dimeric form
Weernink, P. A. O., Rijksen, G., Mascini, E. M., & Saal, G. E. J. (1992) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/0167-4838(92)90337-d · Cited by 20
In vivo factors influencing tumour M2-pyruvate kinase level in human pancreatic cancer cell lines
Kumar, Y., Mazurek, S., Yang, S., Failing, K., Winslet, M. C., Fuller, B. J., & Davidson, B. R. (2010) · Tumor Biology · doi:10.1007/s13277-009-0010-3 · Cited by 19
Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers
Li, X., Zhang, C., Kim, W., Arif, M., Gao, C., Hober, A., Kotol, D., Strandberg, L., Forsström, B., Sivertsson, Å., et al. (2021) · Cancers · doi:10.3390/cancers13020348 · Cited by 20
Tang, D., Subramanian, J., Haley, B., Baker, J. J., Luo, L., Hsu, W., Liu, P., Sandoval, W. N., Laird, M. W., Snedecor, B., et al. (2018) · Biotechnology Journal · doi:10.1002/biot.201800332 · Cited by 17
García, S., Saldana-Caboverde, A., Anwar, M. R., Raval, A. P., Nissanka, N., Pinto, M., Moraes, C. T., & Díaz, F. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab282 · Cited by 18
Fanjul, A. N., & Farı́as, R. N. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54130-2 · Cited by 17
Shimada, N., Takasawa, R., & Tanuma, S.-I. (2017) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2017.12.008 · Cited by 17
Parkin exerts the tumor‐suppressive effect through targeting mitochondria
Sun, X., Ye, G., Mai, Y., Shu, Y., Wang, L., & Zhang, J. (2023) · Medicinal Research Reviews · doi:10.1002/med.21938 · Cited by 17
Metabolic pathways in cancers: key targets and implications in cancer therapy
Vijayakumar, S. N., Sethuraman, S., & Krishnan, U. M. (2015) · RSC Advances · doi:10.1039/c5ra06505d · Cited by 16
Shi, X., You, L., & Luo, R.-Y. (2019) · Physical Biology · doi:10.1088/1478-3975/ab3f5a · Cited by 16
Proteomics revisits the cancer metabolome
Hu, H., Deng, C., Yang, T., Dong, Q. G., Chen, Y., Nice, E. C., Huang, C., & Wei, Y. (2011) · Expert Review of Proteomics · doi:10.1586/epr.11.31 · Cited by 13
Andreazzoli, M., Barravecchia, I., Cesari, C. D., Angeloni, D., & Demontis, G. C. (2021) · Cells · doi:10.3390/cells10092489 · Cited by 14
Yang, Y., Xiang, R., Yang, C., Liu, X., Shen, W., Zuo, J., Chang, Y., & Fang, F. (2009) · Biomedical and Environmental Sciences · doi:10.1016/s0895-3988(10)60012-8 · Cited by 12
Zhang, L., Li, Q., Deng, Y., Zou, Y., Wang, L., & Li, J. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13655 · Cited by 14
A responsive fluorescent probe for detecting and imaging pyruvate kinase M2 in live cells
Zhang, Y., Li, H., Mai, H., Luo, D., Ji, X., Liu, Z., Peng, S., Xu, X., Zhang, Y., Lan, R., et al. (2022) · Chemical Communications · doi:10.1039/d2cc01211a · Cited by 10
Addressing the heterogeneity in liver diseases using biological networks
Lam, S. C. C., Doran, S. F., Yuksel, H. H., Altay, Ö., Türkez, H., Nielsen, J., Borén, J., Uhlén, M., & Mardinoğlu, A. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa002 · Cited by 11
The role of glycolysis in immune response
Budikhina, A. S., & Pashenkov, M. V. (2021) · Immunologiya · doi:10.33029/0206-4952-2021-42-1-5-20 · Cited by 12
Kuo, C.-W., Chen, D., Tsai, M., Lin, C., Cheng, H.-W., Tsay, Y., & Wang, H. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1151359 · Cited by 8
Regeenes, R., Wang, Y., Piro, A., Au, A., Yip, C. M., Wheeler, M. B., & Rocheleau, J. V. (2022) · Biosensors and Bioelectronics X · doi:10.1016/j.biosx.2022.100285 · Cited by 8
Rath, A., Rehberg, M., Janke, R., Genzel, Y., Scholz, S., Noll, T., Rose, T., Sandig, V., & Reichl, U. (2014) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2014.03.012 · Cited by 8
Do We Need a New Hypothesis for KATP Closure in β-Cells? Distinguishing the Baby From the Bathwater
Satin, L. S., Corradi, J., & Sherman, A. (2024) · Diabetes · doi:10.2337/db24-0131 · Cited by 6
The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues
Li, L., Cheng, S., Yeh, Y. A., Shi, Y., Henderson, N., Price, D., Gu, X., & Yu, X. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1392085 · Cited by 6
Structural and kinetic characterization of Trypanosoma congolense pyruvate kinase
Torres, J. E. P., Yuan, M., Goossens, J., Versées, W., Caljon, G., Michels, P. A. M., Walkinshaw, M. D., Magez, S., & Sterckx, Y. G. ‐. (2020) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2020.111263 · Cited by 6
Jacquet, P., & Stéphanou, A. (2023) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2023.111434 · Cited by 6
Quantitative Analysis of Cancer Metabolism: From pSIRM to MFA
Zasada, C., & Kempa, S. (2016) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-319-42118-6_9 · Cited by 5
Citrate oscillations during cell cycle are a targetable vulnerability in cancer cells
Icard, P., Alifano, M., & Simula, L. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189313 · Cited by 4
Obata, T., & Cheng, S.-Y. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91552-2 · Cited by 4
Dimeric PKM2 in chondrocytes impairs mitochondrial homeostasis in osteoarthritis
Liu, B., Liang, Y., Wang, C., Weng, Z., Yang, Y., Shi, Y., & Zhang, C. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08621-4 · Cited by 2
Virtual high-throughput screens identifying hPK-M2 inhibitors: Exploration of model extrapolation
Chen, J. J. F., Schmucker, L. N., & Visco, D. P. (2018) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2018.12.006 · Cited by 2
Arsanilic acid–Sepharose chromatography of pyruvate kinase from KB cells
Huang, R., Yeh, H.-Y., Cheng, S.-C., Chow, L., & Lee, T.-C. (2000) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)00043-8 · Cited by 2
Molecular docking analysis of pyruvate kinase M2 with a potential inhibitor from the ZINC database
Sharma, P. V. (2021) · Bioinformation · doi:10.6026/97320630017139 · Cited by 2
Barlow, J., Crowe, T., & Topliss, D. J. (1997) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-60709-7_13 · Cited by 2
Tumor Cell Energetic Metabolome
Mazurek, S. (2007) · Wiley eBooks · doi:10.1002/9783527621095.ch16 · Cited by 2
Macpherson, J. A., Theisen, A., Masino, L., Fets, L., Driscoll, P. C., Encheva, V., Snijders, A. P., Martin, S. R., Kleinjung, J., Barran, P. E., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/378133 · Cited by 2
Kim, M., Zhang, Y., & Birchmeier, C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.22.424062 · Cited by 2
Li, B., Han, Z., Zhang, J., Meng, T., Zheng, Y., Guan, Y., Qian, L., Chen, Y., Liu, X., Nahar, L., et al. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118150 · Cited by 1
The potential roles of PKM2 in cerebrovascular diseases
Ma, L., Li, H. C., Xu, H., & Liu, D. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112675 · Cited by 2
Small-Molecule Reprogramming of Cancer Metabolism
Pratt, M. R. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.09.001 · Cited by 1
Ashizawa, K., & Cheng, S.-Y. (1992) · Journal of Biochemical and Biophysical Methods · doi:10.1016/0165-022x(94)90081-7 · Cited by 1
Local effects of Linoorbitides and enterolactone On intestinal epithelial functions
Almousa, A. A. (2017) · University Library - University of Saskatchewan (University of Saskatchewan) · Cited by 1
Metabolic patterning and regulation during early embryo development and appendage regeneration
Thomson, C. (2019) · Research Explorer (The University of Manchester) · Cited by 1
Ignacak, J., Wiśniewska-Wrona, M., Dulińska-Litewka, J., Pałka, I., & Kucharska, M. (2014) · Progress on Chemistry and application of Chitin and its Derivatives · doi:10.15259/pcacd.19.04
Investigation of mammalian cell metabolism by quantification of key metabolic enzyme activities
Janke, R. (2012) · MPG.PuRe (Max Planck Society)
Functions of Extracellular Pyruvate Kinase M2 in Tissue Repair and Regeneration
Zhang, Y. (2022) · Digital Archive @ GSU · doi:10.57709/8513687
Study of regulatory mechanisms of glycolytic and gluconeogenic enzymes
Yuan, M. (2016) · Edinburgh Research Archive (University of Edinburgh)
Breast Cancer Stem Cells: Tumourspheres and Implications for Therapy
Morrison, B. J. (2011) · Griffith Research Online · doi:10.25904/1912/1434
Piñeiro, S. M. (2019) · UVaDOC UVaDOC University of Valladolid Documentary Repository (University of Valladolid) · doi:10.35376/10324/38423
Why the tumor cell metabolism is not that abnormalPreprint
Jacquet, P., & Stéphanou, A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/865048
Staff potential Russian customs authorities in the context of integration into the world economy
Сергеевна, Л. А. (2013) · Юридическая наука и практика: Вестник Нижегородской академии МВД России
Chernoff, J. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.13968977.15426086
Kyriakis, J. M. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.13968977.15455088
Data from Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes
Apostolidi, M., Vathiotis, I. A., Muthusamy, V., Gaule, P., Gassaway, B. M., Rimm, D. L., & Rinehart, J. (2023) · doi:10.1158/0008-5472.c.6512994.v1
Wang, J., Zhang, W., Shen, N., Li, P., Xie, W., Wang, S., Cheng, Y., Zhao, L., Yang, Y., & Zhao, H. (2026) · The AAPS Journal · doi:10.1208/s12248-026-01261-8
Mei, M., Miao, Q., Li, M. T., Wang, H., Ding, J., Hu, G., & Wei, Y. (2026) · CNS Neuroscience & Therapeutics · doi:10.1002/cns.70968
Qiang, M., Zhao, Y., Wang, G., Chen, Z., Zhang, F., Wang, Z., Wang, G., Zhuang, C., Ning, S., Yao, J., et al. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.06.029
Yu, W., Sun, R., Lu, X., Deng, Q., Zhang, H., Chen, S., Dai, S., Hu, T., Li, X., Yang, Y., et al. (2026) · Science Immunology · doi:10.1126/sciimmunol.aeb7315
Banerjee, T., & Bose, K. (2026) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2026.101948
Stress-inducible WASF3 regulates brain metabolism and cognitive function
Syed, A. M., Ma, J., Wang, P., Son, Y., Penjweini, R., Mattu, N., Knutson, J. R., Nakamori-Yamashita, S., Springer, D., Ganguly, A., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2617198123
Marini, A. (2014) · UnissResearch (Università degli Studi di Sassari)
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
