pyruvate kinase

Summary

Summary: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.

Top Publications

  1. ncbi The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
    Heather R Christofk
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 452:230-3. 2008
  2. pmc Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses
    Dimitrios Anastasiou
    Beth Israel Deaconess Medical Center, Department of Medicine Division of Signal Transduction, Boston, MA 02115, USA
    Science 334:1278-83. 2011
  3. pmc Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1
    Weibo Luo
    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 145:732-44. 2011
  4. pmc HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
    Charles J David
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 463:364-8. 2010
  5. pmc Serine is a natural ligand and allosteric activator of pyruvate kinase M2
    Barbara Chaneton
    Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK
    Nature 491:458-62. 2012
  6. ncbi Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2
    J Chen
    Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
    Oncogene 30:4297-306. 2011
  7. ncbi Pyruvate kinase M2 is a phosphotyrosine-binding protein
    Heather R Christofk
    Department of Systems Biology
    Nature 452:181-6. 2008
  8. pmc Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA
    Mo Chen
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Cancer Res 70:8977-80. 2010
  9. pmc Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
    Dimitrios Anastasiou
    Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA
    Nat Chem Biol 8:839-47. 2012
  10. pmc Evidence for an alternative glycolytic pathway in rapidly proliferating cells
    Matthew G Vander Heiden
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 329:1492-9. 2010

Detail Information

Publications282 found, 100 shown here

  1. ncbi The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
    Heather R Christofk
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 452:230-3. 2008
    ..Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis...
  2. pmc Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses
    Dimitrios Anastasiou
    Beth Israel Deaconess Medical Center, Department of Medicine Division of Signal Transduction, Boston, MA 02115, USA
    Science 334:1278-83. 2011
    ..cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys(358)...
  3. pmc Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1
    Weibo Luo
    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 145:732-44. 2011
    The pyruvate kinase isoforms PKM1 and PKM2 are alternatively spliced products of the PKM2 gene...
  4. pmc HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
    Charles J David
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 463:364-8. 2010
    ..In mammals, this is partly achieved through control of pyruvate kinase isoform expression...
  5. pmc Serine is a natural ligand and allosteric activator of pyruvate kinase M2
    Barbara Chaneton
    Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK
    Nature 491:458-62. 2012
    ..Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and ..
  6. ncbi Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2
    J Chen
    Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
    Oncogene 30:4297-306. 2011
    ..Here, we showed that shikonin and its analogs are inhibitors of tumor-specific pyruvate kinase-M2 (PKM2), among which shikonin and its enantiomeric isomer alkannin were the most potent and showed ..
  7. ncbi Pyruvate kinase M2 is a phosphotyrosine-binding protein
    Heather R Christofk
    Department of Systems Biology
    Nature 452:181-6. 2008
    ..proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 (fetal) isoform of pyruvate kinase (PKM2), binds directly and selectively to tyrosine-phosphorylated peptides...
  8. pmc Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA
    Mo Chen
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Cancer Res 70:8977-80. 2010
    ..to aerobic glycolysis is partly achieved by a switch in the splice isoforms of the glycolytic enzyme pyruvate kinase. Although normal cells express the pyruvate kinase M1 isoform (PKM1), tumor cells predominantly express the ..
  9. pmc Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
    Dimitrios Anastasiou
    Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA
    Nat Chem Biol 8:839-47. 2012
    ..The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer...
  10. pmc Evidence for an alternative glycolytic pathway in rapidly proliferating cells
    Matthew G Vander Heiden
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 329:1492-9. 2010
    ..The M2 isoform of pyruvate kinase (PKM2) promotes the metabolism of glucose by aerobic glycolysis and contributes to anabolic metabolism...
  11. pmc Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells
    Nana Maria Grüning
    Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany
    Cell Metab 14:415-27. 2011
    ..Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism when ..
  12. pmc Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression
    Michael S Goldberg
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Exp Med 209:217-24. 2012
    ..b>Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms...
  13. pmc Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation
    Jiangbin Ye
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 109:6904-9. 2012
    ..cancer cells display high glycolytic activity, cancer cells selectively express the less active M2 isoform of pyruvate kinase (PKM2)...
  14. ncbi Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells
    Sybille Mazurek
    Institute of Biochemistry and Endocrinology, Veterinary Medicine, University of Giessen, Giessen, Germany
    Int J Biochem Cell Biol 43:969-80. 2011
    ..In tumor cells, the glycolytic pyruvate kinase isoenzyme M2 (PKM2, M2-PK) determines whether glucose is converted to lactate for regeneration of energy (..
  15. pmc Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth
    Qian Sun
    State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China
    Proc Natl Acad Sci U S A 108:4129-34. 2011
    ..For a largely unknown regulatory mechanism, a rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) isoform is exclusively expressed in embryonic, proliferating, and tumor cells, and plays an ..
  16. ncbi Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes
    B Altenberg
    Bioinformatics Group, European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Genomics 84:1014-20. 2004
    ..almost ubiquitously overexpressed, particularly glyceraldehyde-3-phosphate dehydrogenase, enolase 1, and also pyruvate kinase, and those that are overexpressed in less than 50% of the investigated cancers...
  17. pmc Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase
    Xueliang Gao
    Department of Biology, Georgia State University, Atlanta, GA 30303, USA
    Mol Cell 45:598-609. 2012
    b>Pyruvate kinase isoform M2 (PKM2) is a glycolysis enzyme catalyzing conversion of phosphoenolpyruvate (PEP) to pyruvate by transferring a phosphate from PEP to ADP. We report here that PKM2 localizes to the cell nucleus...
  18. pmc Human pyruvate kinase M2: a multifunctional protein
    Vibhor Gupta
    National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
    Protein Sci 19:2031-44. 2010
    ..b>Pyruvate kinase, which catalyzes the last but rate-limiting step of glycolysis, is expressed in four isozymic forms, ..
  19. pmc The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism
    Cynthia V Clower
    Division of Signal Transduction, Department of Systems Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:1894-9. 2010
    ..This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase, in contrast to the M1 isozyme normally expressed in differentiated cells, and it confers a proliferative ..
  20. ncbi Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth
    Lei Lv
    Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University, Shanghai 200032, China
    Mol Cell 42:719-30. 2011
    ..Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and ..
  21. pmc Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth
    Taro Hitosugi
    Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
    Sci Signal 2:ra73. 2009
    ..We found that oncogenic forms of fibroblast growth factor receptor type 1 inhibit the pyruvate kinase M2 (PKM2) isoform by direct phosphorylation of PKM2 tyrosine residue 105 (Y(105))...
  22. pmc No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis
    Katharina Bluemlein
    Max Planck Institute for Molecular Genetics, Berlin, Germany
    Oncotarget 2:393-400. 2011
    ..from a switch in the expression of alternative splice forms (PKM1 and PKM2) of the glycolytic enzyme pyruvate kinase (PK), which is also important for malignant transformation...
  23. pmc Identification of small molecule inhibitors of pyruvate kinase M2
    Matthew G Vander Heiden
    Dana Farber Cancer Institute, Boston, MA 02115, United States
    Biochem Pharmacol 79:1118-24. 2010
    ..Cancer cells universally express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2), and previous work has demonstrated that PKM2 expression is necessary for aerobic glycolysis and cell ..
  24. ncbi Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells
    Mayumi Tamada
    Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan
    Clin Cancer Res 18:5554-61. 2012
    The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells...
  25. pmc Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer
    Jae Yun Lim
    Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135 720, South Korea
    World J Gastroenterol 18:4037-43. 2012
    To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.
  26. ncbi Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis
    Jill D Dombrauckas
    Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Biochemistry 44:9417-29. 2005
    Four isozymes of pyruvate kinase are differentially expressed in human tissue...
  27. pmc Pyruvate kinase M2 is a target of the tumor-suppressive microRNA-326 and regulates the survival of glioma cells
    Benjamin Kefas
    Division of Neuro Oncology, Neurology Department, University of Virginia Health System, Old Medical School, Room 4818, 21 Hospital Drive, Charlottesville, VA 22908, USA
    Neuro Oncol 12:1102-12. 2010
    ..Computational target gene prediction revealed pyruvate kinase type M2 (PKM2) as another target of miRNA-326...
  28. ncbi Measurement of fecal pyruvate kinase type M2 (tumor M2-PK) concentrations in patients with gastric cancer, colorectal cancer, colorectal adenomas and controls
    P D Hardt
    Third Medical Department, Giessen University Hospital, Rodthohl 6, D 35385 Giessen, Germany
    Anticancer Res 23:851-3. 2003
    The determination of Tumor M2 Pyruvate Kinase (Tumor M2-PK) in EDTA plasma has been described as a tumor marker in a variety of different tumor types...
  29. pmc Pyruvate kinase M2 regulates glucose metabolism by functioning as a coactivator for hypoxia-inducible factor 1 in cancer cells
    Weibo Luo
    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, USA
    Oncotarget 2:551-6. 2011
    ..b>Pyruvate kinase M2 (PKM2) contributes to the Warburg effect by previously unknown mechanisms...
  30. pmc PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells
    William J Israelsen
    Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 155:397-409. 2013
    The pyruvate kinase M2 isoform (PKM2) is expressed in cancer and plays a role in regulating anabolic metabolism...
  31. ncbi Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response
    D Turner
    Paediatric Gastroenterology and Nutrition Unit, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, POB 3235, Jerusalem 91031, Israel
    Gut 59:1207-12. 2010
    ..To compare four faecal markers for their ability to predict steroid refractoriness in severe paediatric ulcerative colitis (UC). Construct validity and responsiveness to change were also assessed...
  32. ncbi Lectin-based proteomic profiling of aged skeletal muscle: decreased pyruvate kinase isozyme M1 exhibits drastically increased levels of N-glycosylation
    Kathleen O'Connell
    Department of Biology, National University of Ireland, Maynooth, Co Kildare, Ireland
    Eur J Cell Biol 87:793-805. 2008
    ..b>Pyruvate kinase isoform M1 with protein accession number gi|16757994|, exhibiting a pI of 6...
  33. pmc Characterization of a glucose-repressed pyruvate kinase (Pyk2p) in Saccharomyces cerevisiae that is catalytically insensitive to fructose-1,6-bisphosphate
    E Boles
    Institut fur Mikrobiologie, Heinrich Heine Universitat, Dusseldorf, Germany
    J Bacteriol 179:2987-93. 1997
    ..have characterized the gene YOR347c of Saccharomyces cerevisiae and shown that it encodes a second functional pyruvate kinase isoenzyme, Pyk2p...
  34. ncbi Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply
    Gilles A Spoden
    Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria
    Exp Cell Res 315:2765-74. 2009
    The glycolytic key regulator pyruvate kinase M2 (M2-PK or PKM2) can switch between a highly active tetrameric and an inactive dimeric form. The transition between the two conformations regulates the glycolytic flux in tumor cells...
  35. ncbi Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription
    Jungwoon Lee
    Department of Life Science, Sogang University, Seoul 121 742, Republic of Korea
    Int J Biochem Cell Biol 40:1043-54. 2008
    ..ionization-time-of-flight) MS (mass spectrometry) and isolated a novel Oct-4-interacting protein, pyruvate kinase type M2 (PKM2 or M2-PK)...
  36. ncbi Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death
    Attila Stetak
    Department of Molecular Biology, Max Planck Institute for Biochemistry, Martinsried, Germany
    Cancer Res 67:1602-8. 2007
    ..Moreover, they are able to adapt to hypoxia by changing their glycolytic rate. Pyruvate kinase (PK) is a rate-limiting enzyme in glycolysis that is converted to a less active dimer form of PKM2 isoenzyme ..
  37. ncbi ChREBP rather than USF2 regulates glucose stimulation of endogenous L-pyruvate kinase expression in insulin-secreting cells
    Haiyan Wang
    Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Center, CH 1211 Geneva 4, Switzerland
    J Biol Chem 277:32746-52. 2002
    ..There is controversy whether or not upstream stimulatory factors (USF) regulate the glucose responsiveness of L-pyruvate kinase (L-PK) promoter activity in hepatocytes...
  38. ncbi Quantification of tumor type M2 pyruvate kinase (Tu M2-PK) in human carcinomas
    E Eigenbrodt
    Institute for Biochemistry and Endocrinology, University of Giessen, Germany
    Anticancer Res 17:3153-6. 1997
    Proliferating and tumor cells express a certain isoenzyme of pyruvate kinase, called PK type M2. This isoenzyme can be isolated in an active tetrameric and an inactive dimeric form. We have termed this form tumor type M2-PK...
  39. pmc Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin
    Mohd Askandar Iqbal
    National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
    PLoS ONE 7:e36764. 2012
    Metabolism of cancer cells with pyruvate kinase M2 (PKM2) at its centre stage has assumed a prime significance in cancer research in recent times...
  40. pmc Consequences of phosphoenolpyruvate:sugar phosphotranferase system and pyruvate kinase isozymes inactivation in central carbon metabolism flux distribution in Escherichia coli
    Eugenio Meza
    Cellular Engineering and Biocatalysis Department, Biotechnology Institute, Universidad Nacional Autonoma de Mexico, Apdo Postal 510 3, Cuernavaca, Morelos 62210, Mexico
    Microb Cell Fact 11:127. 2012
    ..W3110 derivative strains that lack the main PEP consumers PEP:sugar phosphotransferase system (PTS-) and pyruvate kinase isozymes PykA and PykF (PTS-pykA- and PTS-pykF-)...
  41. ncbi Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase
    Ben C L Chan
    Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
    J Ethnopharmacol 137:767-73. 2011
    ..The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms...
  42. pmc Pyruvate kinase is a dosage-dependent regulator of cellular amino acid homeostasis
    Katharina Bluemlein
    Department of Biochemistry, University of Cambridge, Cambridge, UK
    Oncotarget 3:1356-69. 2012
    The glycolytic enzyme pyruvate kinase (PK) is required for cancer development, and has been implicated in the metabolic transition from oxidative to fermentative metabolism, the Warburg effect...
  43. ncbi Redirecting carbon flux through exogenous pyruvate kinase to achieve high ethanol yields in Clostridium thermocellum
    Yu Deng
    Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA
    Metab Eng 15:151-8. 2013
    In Clostridium thermocellum, a thermophilic anaerobic bacterium able to rapidly ferment cellulose to ethanol, pyruvate kinase (EC 2.7.1.40) is absent based on both the genome sequence and enzymatic assays...
  44. pmc Molecular targets of a human HNF1 alpha mutation responsible for pancreatic beta-cell dysfunction
    H Wang
    Division de Biochimie Clinique et de Diabétologie Expérimentale, Départment de Médecine Interne, Centre Medical Universitaire, CH 1211 Geneva 4, Switzerland
    EMBO J 19:4257-64. 2000
    ..In addition to reduced expression of the genes encoding insulin, glucose transporter-2, L-pyruvate kinase, aldolase B and 3-hydroxy-3-methylglutaryl coenzyme A reductase, induction of HNF1 alpha-P291fsinsC also ..
  45. pmc Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2
    Mohd Askandar Iqbal
    National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
    Mol Cancer 12:72. 2013
    ..Here, we attempt to understand the role of insulin in promotion of cancer metabolism. To this end, the role of insulin in regulating glycolytic enzyme pyruvate kinase M2 (PKM2) was examined.
  46. ncbi Functional analysis, overexpression, and kinetic characterization of pyruvate kinase from methicillin-resistant Staphylococcus aureus
    Roya Zoraghi
    Division of Infectious Diseases, Department of Medicine, University of BritishColumbia, Vancouver, Britsih Columbia, CanadaV5Z3J5
    Biochemistry 49:7733-47. 2010
    ..Here we report the essentiality and kinetic properties of MRSA pyruvate kinase (PK). Targetron-mediated gene disruption demonstrated PK is essential for S...
  47. pmc Methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as a target for bis-indole alkaloids with antibacterial activities
    Roya Zoraghi
    Division of Infectious Diseases, Department of Medicine, University of British Columbia, British Columbia, Vancouver V5Z 3J5, Canada
    J Biol Chem 286:44716-25. 2011
    ..We have recently identified pyruvate kinase (PK) as a potential novel drug target based upon it being an essential hub in the MRSA interactome (Cherkasov,..
  48. ncbi The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters
    T Noguchi
    Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Japan
    J Biol Chem 262:14366-71. 1987
    cDNA clones for rat R-type pyruvate kinase and a genomic clone encoding both L- and R-type isozyme mRNAs were isolated...
  49. ncbi Fecal M2-pyruvate kinase (M2-PK): a novel marker of intestinal inflammation
    Guy Chung-Faye
    Department of Gastroenterology, King s College Hospital, London, UK
    Inflamm Bowel Dis 13:1374-8. 2007
    ..The dimeric M2-isoform of pyruvate kinase (M2-PK) has been reported to be elevated in fecal specimens from colorectal cancer (CA) patients, but its ..
  50. pmc 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase
    Martin J Walsh
    NIH Chemical Genomics Center, NIH Center for Translational Therapeutics, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, USA
    Bioorg Med Chem Lett 21:6322-7. 2011
    ..cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism...
  51. pmc Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer
    P D Hardt
    Third Medical Department and Policlinic, Giessen University Hospital, Justus Liebig University of Giessen, Rodthohl 6, Giessen 35392, Germany
    Br J Cancer 91:980-4. 2004
    Proliferating cells, especially tumour cells, express a special isoenzyme of pyruvate kinase, termed M2-PK, which can occur in a tetrameric form with a high affinity to its substrate, phosphoenolpyruvate (PEP), and in a dimeric form with ..
  52. pmc SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions
    Kirstie E Keller
    Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA
    Science 338:1069-72. 2012
    b>Pyruvate kinase isoform M2 (PKM2) plays an important role in the growth and metabolic reprogramming of cancer cells in stress conditions...
  53. pmc Emerging metabolic targets in cancer therapy
    Yuhua Zhao
    Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
    Front Biosci (Landmark Ed) 16:1844-60. 2011
    ..Here we provide an overview of the current understanding of the Warburg effect upon tumor cell growth and survival, and discussion on the potential metabolic targets for cancer therapy...
  54. ncbi The allosteric regulation of pyruvate kinase
    G Valentini
    Department of Genetics and Microbiology, University of Pavia, via Abbiategrasso 207, 27100 Pavia, Italy
    J Biol Chem 275:18145-52. 2000
    b>Pyruvate kinase (PK) is critical for the regulation of the glycolytic pathway...
  55. ncbi The reverse Warburg effect: glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts
    Gloria Bonuccelli
    Department of Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA
    Cell Cycle 9:1960-71. 2010
    ..We also identify the stromal expression of PKM2 and LDH-B as new candidate biomarkers for the "Reverse Warburg Effect" or "Stromal-Epithelial Metabolic Coupling" in human breast cancers...
  56. ncbi Efficacy of RNAi targeting of pyruvate kinase M2 combined with cisplatin in a lung cancer model
    Wenhao Guo
    State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People s Republic of China
    J Cancer Res Clin Oncol 137:65-72. 2011
    b>Pyruvate kinase isoenzyme M2 (PKM2) is a key enzyme in aerobic glycolysis; inhibition of PKM2 leads to the tumor growth inhibition...
  57. pmc New roles for pyruvate kinase M2: working out the Warburg effect
    Emily C Ferguson
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Trends Biochem Sci 33:359-62. 2008
    ..Two recent studies demonstrate that an embryonic- and cancer-cell-specific isoform of the enzyme pyruvate kinase M2 (PKM2) is regulated by binding to phospho-tyrosine motifs and promotes increased cell growth and tumor ..
  58. ncbi The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing
    T Noguchi
    J Biol Chem 261:13807-12. 1986
    The complete nucleotide sequences of rat M1- and M2-type pyruvate kinase mRNAs were determined by sequencing the cDNAs and by analyses of S1 nuclease mapping and primer extension...
  59. pmc Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth
    Barbara Chiavarina
    Departments of Stem Cell Biology and Regenerative Medicine and Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
    Cancer Biol Ther 12:1101-13. 2011
    ..To this end, normal human fibroblasts were genetically-engineered to express the two isoforms of pyruvate kinase M (PKM1 and PKM2), a key enzyme in the glycolytic pathway...
  60. ncbi Pyruvate kinase type M2 and its role in tumor growth and spreading
    Sybille Mazurek
    Institute of Biochemistry and Endocrinology, Veterinary Faculty, University of Giessen, Frankfurter Strasse 100, 35392 Giessen, Germany
    Semin Cancer Biol 15:300-8. 2005
    Proliferating cells and tumor cells in particular express the pyruvate kinase isoenzyme type M2 (M2-PK)...
  61. pmc Evaluation of substituted N,N'-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase
    Matthew B Boxer
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, MSC 3370 Bethesda, Maryland 20850, USA
    J Med Chem 53:1048-55. 2010
    ..Pharmacological activators of a tumor cell specific pyruvate kinase isozyme (PKM2) may be an approach for altering the classic Warburg effect characteristic of aberrant ..
  62. pmc ADP compartmentation analysis reveals coupling between pyruvate kinase and ATPases in heart muscle
    Mervi Sepp
    Laboratory of Systems Biology, Institute of Cybernetics, Tallinn University of Technology, Tallinn, Estonia
    Biophys J 98:2785-93. 2010
    ..In addition, our experimental data show that considerable activity of endogenous pyruvate kinase (PK) remains in the cardiomyocytes after permeabilization...
  63. pmc Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein
    T Kawaguchi
    Department of Biochemistry, Dallas Veterans Affairs Medical Center and University of Texas Southwestern Medical Center at Dallas, 4500 South Lancaster Road, Dallas, TX 75223, USA
    Proc Natl Acad Sci U S A 98:13710-5. 2001
    ..transcription factor from rat liver binding to the carbohydrate responsive element of the L-type pyruvate kinase (L-PK) gene. This factor was named carbohydrate responsive element binding protein (ChREBP)...
  64. ncbi Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice
    Hua Shan Shi
    Department of Thoracic Oncology, Sichuan University, Chengdu, China
    Cancer Sci 101:1447-53. 2010
    ..b>Pyruvate kinase isoenzyme M2 (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells...
  65. pmc Understanding the role of PknJ in Mycobacterium tuberculosis: biochemical characterization and identification of novel substrate pyruvate kinase A
    Gunjan Arora
    Institute of Genomics and Integrative Biology CSIR, Delhi, India
    PLoS ONE 5:e10772. 2010
    ..tuberculosis membrane-associated protein fraction is treated with the active kinase and glycolytic enzyme Pyruvate kinase A (mtPykA) is identified as one of the potential substrates of PknJ...
  66. pmc Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutaminolysis: role of pyruvate kinase type M2 and the glycolytic-enzyme complex
    S Mazurek
    Institute for Biochemistry and Endocrinology, Veterinary Faculty, University of Giessen, Frankfurter Strasse 100, D 35392 Giessen, Germany
    Biochem J 356:247-56. 2001
    Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK), which occurs in a highly active tetrameric form and in a dimeric form with low affinity for phosphoenolpyruvate...
  67. ncbi Tumor type M2 pyruvate kinase expression in advanced breast cancer
    D Luftner
    Schwerpunkt Onkologie und Hamatologie, Universitatsklinikum Charite, Campus Mitte, Humboldt Universitat Berlin, Schumannstr 20 21, 10117 Berlin, Germany
    Anticancer Res 20:5077-82. 2000
    Recently, a high validity correlation of the tumor M2 pyruvate kinase (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been demonstrated in solid tumors...
  68. ncbi Pyruvate kinase deficiency and malaria
    Kodjo Ayi
    McLaughlin Rotman Centre for Global Health, University Health Network Toronto General Hospital, Toronto
    N Engl J Med 358:1805-10. 2008
    ..In humans, pyruvate kinase deficiency is the second most common erythrocyte enzyme disorder...
  69. ncbi Death-associated protein kinase increases glycolytic rate through binding and activation of pyruvate kinase
    I Mor
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:683-93. 2012
    ..In this study, we report that DAPk directly binds and functionally activates pyruvate kinase M2 (PKM2), a key glycolytic enzyme, which contributes to the regulation of cancer cell metabolism...
  70. ncbi Tumor M2-pyruvate kinase in lung cancer patients: immunohistochemical detection and disease monitoring
    Joachim Schneider
    Institut und Poliklinik für Arbeits und Sozialmedizin, Justus Liebig Universitat, Giessen, Germany
    Anticancer Res 22:311-8. 2002
    ..A reliable diagnosis and follow-up of patients is important support for a successful therapy. The diagnostic efficiency of a new marker Tumor M2-pyruvate kinase (Tumor M2-PK) is evaluated.
  71. ncbi Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation
    Gilles A Spoden
    Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria
    Int J Cancer 123:312-21. 2008
    Tumor cells express the glycolytic regulator pyruvate kinase subtype M2 (M2-PK), which can occur in a tetrameric form with high affinity to its substrate phosphoenolpyruvate (PEP) and a dimeric form with a low PEP affinity...
  72. ncbi SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity
    Wei Yen Wei
    Graduate Institute of Molecular and Cellular Biology, Tzu Chi University, Hualien, Taiwan
    Arch Virol 157:635-45. 2012
    ..b>Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment...
  73. pmc Structural and functional analysis of pyruvate kinase from Corynebacterium glutamicum
    M S Jetten
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Appl Environ Microbiol 60:2501-7. 1994
    b>Pyruvate kinase activity is an important element in the flux control of the intermediate metabolism...
  74. pmc Identification of pyruvate kinase in methicillin-resistant Staphylococcus aureus as a novel antimicrobial drug target
    Roya Zoraghi
    Department of Medicine, Centre for High Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada
    Antimicrob Agents Chemother 55:2042-53. 2011
    ..Using the architecture of the MRSA interactome, we identified pyruvate kinase (PK) as a potential novel drug target based upon it being a highly connected, essential hub in the MRSA ..
  75. ncbi Isolation and characterization of the human pyruvate kinase M gene
    M Takenaka
    Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Japan
    Eur J Biochem 198:101-6. 1991
    Genomic clones containing the human pyruvate kinase M (PKM) gene, which encodes the M1-type and M2-type isozymes, were isolated and their exon sequences were determined...
  76. ncbi Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells
    Cheng fu Zhou
    Department of Surgery, Zhongshan Hospital, Fudan University School of Medicine, Shanghai 200032, China
    IUBMB Life 64:775-82. 2012
    b>Pyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors...
  77. pmc The metabolic marker tumour pyruvate kinase type M2 (tumour M2-PK) shows increased expression along the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's oesophagus
    K Koss
    Department of Gastroenterology, University Hospital Birmingham, Edgbaston, Birmingham B15 2TH, UK
    J Clin Pathol 57:1156-9. 2004
    Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK)...
  78. ncbi Pyruvate kinase M2 promotes the growth of gastric cancer cells via regulation of Bcl-xL expression at transcriptional level
    Oh Hyung Kwon
    Medical Genomics Research Center, KRIBB, Daejeon 305 806, Republic of Korea
    Biochem Biophys Res Commun 423:38-44. 2012
    PKM2 is an isoenzyme of the glycolytic enzyme pyruvate kinase that promotes aerobic glycolysis. Here, we describe an important role for PKM2 in regulating the survival of gastric cancer (GC) cells...
  79. ncbi Genetic diversity in human erythrocyte pyruvate kinase
    J Berghout
    Department of Biochemistry, McGill University, Complex Traits Group, Montreal, Canada
    Genes Immun 13:98-102. 2012
    Previously, we have shown that pyruvate kinase, liver and red cell isoform (PKLR) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced PKLR function protects human erythrocytes against Plasmodium ..
  80. pmc Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase
    Jian Kang Jiang
    NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, USA
    Bioorg Med Chem Lett 20:3387-93. 2010
    ..Activation of the tumor specific M2 form of pyruvate kinase (PKM2) is a potential strategy for returning cancer cells to a metabolic state characteristic of normal cells...
  81. ncbi The molecular basis of canine pyruvate kinase deficiency
    K M Whitney
    Scott Ritchey Research Center, College of Veterinary Medicine, Auburn University, AL 36849
    Exp Hematol 22:866-74. 1994
    Inherited hemolytic anemia due to pyruvate kinase (PK) deficiency is an autosomal recessive disease of the Basenji dog that closely resembles human PK deficiency...
  82. ncbi The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2
    Gilles A Spoden
    Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria
    J Cell Biochem 107:293-302. 2009
    b>Pyruvate kinase M2 (M2-PK) controls the rate-limiting step at the end of the glycolytic pathway in normal proliferating and tumor cells. Other functions of M2-PK in addition to its role in glycolysis are little understood...
  83. ncbi Pyruvate kinase isoenzyme shift from L-type to M2-type is a late event in hepatocarcinogenesis induced in rats by a choline-deficient/DL-ethionine-supplemented diet
    H J Hacker
    Division of Cell Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Carcinogenesis 19:99-107. 1998
    ..The L and M2 isoenzymes of pyruvate kinase were immunocytochemically demonstrated in liver sections...
  84. ncbi A novel C-terminal proteolytic processing of cytosolic pyruvate kinase, its phosphorylation and degradation by the proteasome in developing soybean seeds
    Guo Qing Tang
    US Department of Agriculture, Agricultural Research Service, North Carolina State University, Raleigh, NC 27695 7631, USA
    Plant J 34:77-93. 2003
    Cytosolic pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) is an important glycolytic enzyme, but the post-translational regulation of this enzyme is poorly understood...
  85. ncbi Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish
    H Kanno
    Okinaka Memorial Institute for Medical Research, Tokyo, Japan
    Blood 83:2311-6. 1994
    We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania...
  86. ncbi Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase
    Akemi Hoshino
    Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 282:17706-11. 2007
    ..trap, a reporter gene-based system to detect inducible nuclear translocation, we found that the M2 isoform of pyruvate kinase, a key enzyme in glycolysis, translocates into the nucleus by interleukin-3, but not by epidermal growth ..
  87. ncbi Opposite pathobiochemical fate of pyruvate kinase and adenylate kinase in aged rat skeletal muscle as revealed by proteomic DIGE analysis
    Philip Doran
    Department of Biology, National University of Ireland, Maynooth, County Kildare, Ireland
    Proteomics 8:364-77. 2008
    ..In contrast to decreased levels of pyruvate kinase (PK), enolase and phosphofructokinase, the mitochondrial ATP synthase, succinate dehydrogenase, malate ..
  88. ncbi Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia
    Giovanna Valentini
    Dipartimento di Genetica e Microbiologia, Universita di Pavia, via Abbiategrasso 207, 27100 Pavia, Italy
    J Biol Chem 277:23807-14. 2002
    ..Characterization of mutant proteins may serve as a valuable tool to assist with diagnosis and genetic counseling...
  89. pmc Diffusion restrictions surrounding mitochondria: a mathematical model of heart muscle fibers
    Hena R Ramay
    Laboratory of Systems Biology, Institute of Cybernetics, Tallinn University of Technology, Tallinn, Estonia
    Biophys J 97:443-52. 2009
    ..Such a low level of permeability indicates that the proteins should play a dominant part in formation of the diffusion restrictions...
  90. pmc A novel GDP-dependent pyruvate kinase isozyme from Toxoplasma gondii localizes to both the apicoplast and the mitochondrion
    Tomoya Saito
    Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160 8582, Japan
    J Biol Chem 283:14041-52. 2008
    We previously reported a cytosolic pyruvate kinase (EC 2.7.1.40) from Toxoplasma gondii (TgPyKI) that differs from most eukaryotic pyruvate kinases in being regulated by glucose 6-phosphate rather than fructose 1,6-diphosphate...
  91. ncbi Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein
    Nobukazu Shimada
    Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3 1 1 Koyadai, Tsukuba, Ibaraki 305 0074, Japan
    Genes Cells 13:245-54. 2008
    ..Here, we have shown that cytoplasmic PML (cPML) directly interacts with M2-type pyruvate kinase (PKM2), a key regulator of carbon fate...
  92. ncbi Quantitative proteome analysis of multidrug resistance in human ovarian cancer cell line
    Sang Lin Li
    Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education of China, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
    J Cell Biochem 109:625-33. 2010
    ..These data will be valuable for further study of the mechanisms of MDR in the ovarian cancer...
  93. ncbi Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling
    Thian Sze Wong
    Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
    Int J Cancer 123:251-7. 2008
    ..Computational target gene prediction suggested that both miR-133a and miR-133b are targeting transcript of pyruvate kinase type M2 (PKM2), a potential oncogene in solid cancers...
  94. pmc Regulation of rat hepatic L-pyruvate kinase promoter composition and activity by glucose, n-3 polyunsaturated fatty acids, and peroxisome proliferator-activated receptor-alpha agonist
    Jinghua Xu
    Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA
    J Biol Chem 281:18351-62. 2006
    ..HNF-4alpha) are key transcription factors involved in the glucose-mediated induction of hepatic L-type pyruvate kinase (L-PK) gene transcription...
  95. ncbi c-Myc and ChREBP regulate glucose-mediated expression of the L-type pyruvate kinase gene in INS-1-derived 832/13 cells
    J Jason Collier
    Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, E1147 BST, 200 Lothrop St, Pittsburgh, PA 15261, USA
    Am J Physiol Endocrinol Metab 293:E48-56. 2007
    ..a necessity in hepatocytes for c-Myc in the regulation of a prototypical glucose-responsive gene, L-type pyruvate kinase (L-PK) (Collier JJ, Doan TT, Daniels MC, Schurr JR, Kolls JK, Scott DK. J Biol Chem 278: 6588-6595, 2003)...
  96. ncbi In vivo effect of Trigonella foenum graecum on the expression of pyruvate kinase, phosphoenolpyruvate carboxykinase, and distribution of glucose transporter (GLUT4) in alloxan-diabetic rats
    Sameer Mohammad
    Hormone and Drug Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
    Can J Physiol Pharmacol 84:647-54. 2006
    Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, ..
  97. ncbi Glucose-6-phosphate dehydrogenase and red cell pyruvate kinase deficiency in neonatal jaundice cases in egypt
    Mohammed Abdel Fattah
    Department of Pediatrics, Cairo University, Cairo, Egypt
    Pediatr Hematol Oncol 27:262-71. 2010
    ..Neonatal red cell pyruvate kinase (PK) deficiency may cause clinical patterns, ranging from extremely severe hemolytic anemia to moderate ..
  98. ncbi [Pyruvate kinase M2 (tumor M2-PK) as a screening tool for colorectal cancer (CRC). A review of current published data]
    N Ewald
    Third Medical Department, University Hospital Giessen, Germany
    Z Gastroenterol 43:1313-7. 2005
    ..Therefore, evaluation of additional screening tools seems to be of great interest. Recently testing for fecal occult blood (FOBT), genetic alterations or alterations in tumor metabolism (e.g., tumor M2-PK) are under investigation...
  99. ncbi Hematologically important mutations: red cell pyruvate kinase (1st update)
    L Baronciani
    Divisione di Ematologia and Centro Trasfusionale e di Immunologia dei Trapianti, I R C C S Ospedale Maggiore, Milano, Italy
    Blood Cells Mol Dis 22:259-64. 1996
  100. pmc Decreased expression of cytosolic pyruvate kinase in potato tubers leads to a decline in pyruvate resulting in an in vivo repression of the alternative oxidase
    Sandra N Oliver
    Max Planck Institute of Molecular Plant Physiology, 14476 Potsdam Golm, Germany
    Plant Physiol 148:1640-54. 2008
    The aim of this work was to investigate the effect of decreased cytosolic pyruvate kinase (PKc) on potato (Solanum tuberosum) tuber metabolism...
  101. ncbi Tumor M2 pyruvate kinase: a tumor marker and its clinical application in gastrointestinal malignancy
    Philip D Hardt
    Third Medical Department and Policlinic, University Hospital Giessen and Marburg, Giessen Site, Rodthohl 6, D 35392, Giessen, Germany
    Expert Rev Mol Diagn 8:579-85. 2008
    Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed Tumor M2 pyruvate kinase...

Research Grants62

  1. PKM2 inhibition and redox regulation in chemoprevention
    Yunfeng Zhao; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The major goal of this project is to determine whether targeting pyruvate kinase M2 (PKM2), the enzyme in the last step of glycolysis, can serve as a novel chemopreventive approach...
  2. Role of adipose protein-tyrosine phosphatase 1B in glucose homeostasis and body m
    FAWAZ GEORGE HAJ; Fiscal Year: 2013
    ..iv) Indentify pyruvate kinase M2 as a novel substrate of PTP1B...
  3. Glycolysis and Glutamate Storage into Synaptic Vesicles
    Tetsufumi Ueda; Fiscal Year: 2010
    ..More recently we have obtained preliminary evidence that pyruvate kinase (PK), another glycolytic enzyme capable of ATP synthesis, is also bound to synaptic vesicles, and that ..
  4. Development of normal and dystrophic canine iPS lines
    COLIN EDWARD BISHOP; Fiscal Year: 2010
    ..von Willebrand disease, severe combined immunodeficiency disorder, X-linked Duchenne type muscular dystrophy, pyruvate kinase deficiency, muscle type phosphofructokinase deficiency, hemophilia and narcolepsy...
  5. The Role of NPM-ALK Signaling in Tumor Cell Metabolism
    SCOTT RP MCDONNELL; Fiscal Year: 2012
    ..We specifically identified Pyruvate Kinase M2 (PKM2) as a candidate protein of NPM-ALK regulation and metabolic influence...
  6. Metabolic regulators in the mechanisms of caloric restriction
    Rozalyn M Anderson; Fiscal Year: 2013
    ..and iii) the role of the RNA binding motif of PGC-11 in regulating the pro-respiration splice variant of pyruvate kinase. Specific Aim 3: To determine the impact of factors involved in mitochondrial adaptation on WAT and serum ..
  7. Dissecting Allostery in Pyruvate Kinase
    Aron W Fenton; Fiscal Year: 2012
    ..Activating human liver pyruvate kinase (hL-PYK) increases glucose catabolism by glycolysis and is therefore an antihyperglycemic drug target, a ..
  8. Tyrosine Kinase Signaling in Cancer Cell Metabolism
    Jing Chen; Fiscal Year: 2013
    ..These protein factors include pyruvate kinase M2 (fetal) isoform (PKM2), lactate dehydrogenase A (LDH-A), and pyruvate dehydrogenase kinase 1 (PDHK1), ..
  9. DEVELOPMENT EFFECT ON LOOP DIURETIC OTOTOXICITY
    Leonard Rybak; Fiscal Year: 1999
    ..the cochlea on the activities of key glycolytic enzymes, hexokinase (HK) 6-phosphofructo-1-kinase (PKE) and pyruvate kinase (PK). Preliminary experiments have demonstrated that furosemide is a potent noncompetitive inhibitor of PFK...
  10. Inhibitors Against Trypanosomatid Pyruvate Kinases
    MALCOLM DOUGLAS WALKINSHAW; Fiscal Year: 2012
    ..provided by applicant): The goal of this project is to discover and optimize selective inhibitors of pyruvate kinase (PYK) from two protist parasites: Trypanosoma cruzi causes Chagas'disease throughout the Americas, ..
  11. Stem Cell Gene Therapy for Pyruvate Kinase Deficiency Using Foamy Vectors
    Grant Trobridge; Fiscal Year: 2009
    ..Here we propose to overcome these problems by developing a HSC gene therapy for pyruvate kinase (PK) deficiency using foamy retrovirus vectors, and by developing means to target integration of foamy ..
  12. Ras and Tor Signaling in Yeast
    James R Broach; Fiscal Year: 2013
    ..We have recently dissected the role of allosteric and signal-mediated posttranslational regulation of pyruvate kinase, the key constriction point in carbon catabolism, and showed that both processes collaborate to provide ..
  13. Mechanisms of alternative splicing of pre-mRNA
    James L Manley; Fiscal Year: 2013
    ..3. Splicing and disease. Experiments to investigate regulation of pyruvate kinase M-form (PKM) AS in cancer will be continued...
  14. The Mechanisms of PKM2-Regulated Gene Expression in Tumor Development.
    Zhimin Lu; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Pyruvate kinase isozyme type M2 (PKM2), which regulates the rate-limiting final step of glycolysis, is instrumental in tumorigenesis...
  15. Metabolic functions of adipose pyruvate kinase M2
    Ahmed Bettaieb; Fiscal Year: 2013
    Project Summary/Abstract Pyruvate kinase M2 (PKM2) is primarily a tetrameric enzyme that catalyzes the transfer of a phosphate from phosphoenolpyruvate to ADP, resulting in pyruvate and ATP...
  16. Regulation of glucose metabolism to allow tumor initiation and growth
    MATTHEW VANDER HEIDEN; Fiscal Year: 2013
    ..The M2 isoform of pyruvate kinase (PKM2) promotes glucose use for anabolic processes and is the pyruvate kinase isoform found in all human ..
  17. Regulation of nuclear Beta-catenin in EGFR-promoted tumor development.
    Zhimin Lu; Fiscal Year: 2013
    ..b>Pyruvate kinase isozyme type M2 (PKM2), which regulates the rate-limiting final step of glycolysis, is instrumental for ..
  18. PROTEIN KINASE SIGNALING PATHWAYS
    Lewis C Cantley; Fiscal Year: 2012
    ..Kinase C delta and Protein Kinase C theta and, surprisingly, the regulatory domain of the M2 isoform of pyruvate kinase. During the next granting period we intend to use these and other approaches to identify additional protein ..
  19. Metabolic Adaptations of Photoreceptors
    JAMES BRYANT HURLEY; Fiscal Year: 2013
    ..out aerobic glycolysis, prefer glutamine as a fuel for their mitochondria and they express a unique form of pyruvate kinase, PKM2 that can be regulated by tyrosine phosphorylation...
  20. Alternative Splicing of Pyruvate Kinase M: Regulation and Significance in Cancer
    CYNTHIA CLOWER; Fiscal Year: 2011
    ..Significantly, recent work in our lab demonstrates that expression of the pyruvate kinase-M2 (PK-M2) isoform is necessary for this metabolic phenotype...
  21. HORMONAL REGULATION OF ENERGY METABOLISM
    Tarun Patel; Fiscal Year: 1993
    ..studies with various pharmacological agents which modulate cellular cGMP content along with measurements of pyruvate kinase activity and the cellular content of fructose 1,6-and 2,6- bisphosphate will indicate the role of cGMP in ..
  22. Understanding the role of altered metabolism in gliomagenesis
    Russell O Pieper; Fiscal Year: 2013
    ..Two metabolic enzymes, hexokinase (HK) and pyruvate kinase (PK) are key regulators of the metabolic changes that accompany tumorigenesis...
  23. Cellular Metabolites Regulating Cancer-Specific Metabolic Isozymes
    Young Sam Lee; Fiscal Year: 2013
    ..Our preliminary data indicate that (1) SACIAR isozyme-selectively stimulates pyruvate kinase M2 (PKM2), one of a few metabolic enzymes found to be required for tumor growth in xenograft experiments and ..
  24. Dynamic interactions between stem cell and their niche
    David T Scadden; Fiscal Year: 2012
    ..The studies to date have included focused manipulation of pyruvate kinase isoforms (PK-M1 and -M2) implicated in the Warburg effect of solid tumors using engineered mouse models...
  25. FRUCTOFURANOSE MODULATORS--STRUCTURAL/ENZYMATIC STUDIES
    EZZAT YOUNATHAN; Fiscal Year: 1992
    ..Its active form was shown to be the 1,6-bisphosphate which activates phosphofructokinase and pyruvate kinase and simultaneously inhibits the gluconeogenic enzyme fructose 1,6-bisphosphatase...
  26. DYSFUNCTION OF POSTISCHEMIC MYOCARDIUM
    Lewis Becker; Fiscal Year: 2000
    ..to prevent a marked rise in myocardial [Ca2+]i, (2) all of the glycolytic enzymes from aldolase to pyruvate kinase (PK) are bound to SR and are functionally coupled to the Ca2+-ATPase...
  27. REGULATION OF GENE EXPRESSION BY INSULIN-MIMETIC AGENTS
    Susan Stapleton; Fiscal Year: 1992
    ..hepatoma cells, the induction of the glucose transporter mRNA in NIH 3T3 fibroblasts, the induction of L-type pyruvate kinase mRNA in rat hepatocytes and the increase in pancreatic amylase mRNA in the streptozotocin-induced diabetic ..
  28. CONTROL OF GENE TRANSCRIPTION BY ESSENTIAL FATTY ACIDS
    Thomas Gettys; Fiscal Year: 2005
    ..response element and a DR-1 that binds HNF-4 and PPARg and in this sense is similar to the PUFA-RR of the pyruvate kinase gene...
  29. Design & Development of Allosteric effectors of PK
    DONALD ABRAHAM; Fiscal Year: 2004
    Our collaborators and we have successfully cloned and overexpressed human erythrocyte pyruvate kinase (R-PK)...
  30. Engineering proteins to target repair of human disease-causing mutations
    Umut Ulge; Fiscal Year: 2009
    ..We will focus on pyruvate kinase deficiency (PKD) as a model disease...
  31. PATHOPHYSIOLOGY OF HEMOLYSIS: RBC HYDRATION DISORDERS
    Bertil Glader; Fiscal Year: 1980
    ..dehydration will be compared in RBCs from patients with hereditary hemolytic anemias (hereditary xerocytosis, pyruvate kinase deficiency), and several in vitro models...
  32. Hydrogen Peroxide Sensing by Human Endothelial Cells
    James Stone; Fiscal Year: 2006
    ..nuclear ribonucleoprotein (hnRNP) C1/C2, and also stimulate the post-translational modification of pyruvate kinase M2 with alteration of its enzymatic activity...
  33. PHYSIOLOGICAL FUNCTION OF THE S14 PROTEIN
    WILLIAM KINLAW; Fiscal Year: 2000
    ..We found a functional interaction with the proximal 197 bp of the promoter of the gene coding liver-type pyruvate kinase (L-PK), a key regulatory enzyme for provision of substrate for lipogenesis...
  34. TRANSCRIPTIONAL CONTROL OF CARBOHYDRATE RESPONSIVE GENES
    David Rhoads; Fiscal Year: 2002
    ..in the carbohydrate-response elements in the promoters of two other carbohydrate-responsive genes--liver pyruvate kinase and sucrase- isomaltase, which we have also shown to exhibit diurnal periodicity--indicates that HNF-1 may ..
  35. FORMATION AND SURVIVAL OF RED BLOOD CELLS
    Ernest Beutler; Fiscal Year: 2001
    ..abnormalities of erythrocyte metabolism: Mutations affecting glucose-6-phosphate dehydrogenase (G6PD), pyruvate kinase (PK), glucose phosphate isomerase (GPI), and triosephosphate isomerase (TPI)...
  36. PHYSICAL STUDIES OF PROTEIN INTERACTIONS
    James Lee; Fiscal Year: 1992
    ..of this program is elucidate the structure- function correlation for two allosteric enzymes - rabbit muscle pyruvate kinase (PK) and phosphofructokinase (PFK). Towards that goal in the PK system, 4 specific projects are proposed...
  37. Tumor pyruvate kinase as key regulator of cancer metabolism
    FABIAN VOLKER FILIPP; Fiscal Year: 2013
    The project seeks to understand the role of pyruvate kinase as regulator of cancer metabolism...
  38. REGULATION OF LIPOGENESIS BY POLYUNSATURATED FATS
    Steven Clarke; Fiscal Year: 1980
    ..This effect is independent of type or amount of carbohydrate consumed. Phosphofructokinase and pyruvate kinase activities are not influenced by PUFA, which indicates PUFA action is specific for lipogenesis...
  39. MECHANISM OF SUPPRESSION OF SP3 GENE EXPRESSION IN MS
    John Richert; Fiscal Year: 2000
    ..reductase, and elastin, while Sp3 activates TGF-beta, cyclin-dependent kinase inhibitor p21, and pyruvate kinase M genes...
  40. PYRUVATE KINASE AND DEVELOPMENT IN MUCOR
    JOHN PAZNOKAS; Fiscal Year: 1980
    ..I have observed that in one differentiated state, (mycelia,) either of the two isozymes of pyruvate kinase may be found depending on the presence or absence of hexose...
  41. A gene therapy for the treatment of Type 1 diabetes
    Ji Won Yoon; Fiscal Year: 2002
    ..biologically active insulin activity without processing, under the control of the hepatocyte-specific L-type pyruvate kinase promoter (rAAV-LPK-SIA), which regulates SIA expression in response to blood glucose levels...
  42. THE MECHANISM OF RED CELL AGING-HEMOLYTIC ANEMIAS
    Sergio Piomelli; Fiscal Year: 1990
    ..We will study in great detail two key enzymes of glycolysis - hexokinase and pyruvate kinase. We will attempt to clarify their molecular structure and to assess the role played by isozymic shifts in the ..
  43. MUTAGENESIS OF PAPOVAVIRUS TRANSFORMING PROTEINS
    Alan Smith; Fiscal Year: 1990
    ..plan to produce fragments of large-T and chimaeric proteins including parts of large-T or middle-T fused to pyruvate kinase and parts of murine polyoma virus middle-T fused to equivalent sequences from small-t SV40 and middle-T of ..
  44. Discovery of Lead Compounds Against Trypanosomiasis and Leishmaniasis Through Ind
    Malcolm Walkinshaw; Fiscal Year: 2009
    ..research will provide the foundation for the discovery and optimization of selective inhibitors of pyruvate kinase (PYK) of trypanosomatid parasites (Trypanosoma brucei, T. cruzi and Leishmania species)...
  45. METABOLIC AND BIOCHEMICAL STUDIES OF BLOOD CELLS
    Kouichi Tanaka; Fiscal Year: 1990
    ..The objectives are to extend knowledge of pyruvate kinase deficiency and other enzyme deficiency hemolytic anemias with particular reference to genetic polymorphism, ..
  46. INSULIN PRODUCING VECTORS FOR GENE THERAPY OF DIABETES
    MICHAEL RIPPS; Fiscal Year: 2003
    ..hepatocytes and intestinal epithelial cells in vivo using an insulin gene construct driven by the liver-type pyruvate kinase (L-PK) promoter...
  47. Tumor pyruvate kinase as key regulator of cancer metabolism
    FABIAN VOLKER FILIPP; Fiscal Year: 2012
    ..DESCRIPTION (provided by applicant): None provided. ..
  48. Mouse Models to Evaluate the Role of Pyruvate Kinase Regulation in Cancer Biology
    MATTHEW VANDER HEIDEN; Fiscal Year: 2009
    ..enzymes with increased expression in cancer cells is the M2 isoform of the rate-limiting glycolytic enzyme, pyruvate kinase. In contrast to most adult tissues which express the M1 isoform, all cancer cells studied to date exclusively ..
  49. Gene Replacement Therapy in Induced Pluripotent Stem (iPS) Cells for Treatment of
    Tim Townes; Fiscal Year: 2009
    ..In Project 2 (Canine iPS Cells For Pyruvate Kinase Gene Replacement), Dr...
  50. Cytokine signal transduction in immune system
    Hodaka Fujii; Fiscal Year: 2007
    ..The initial screening of cDNA library revealed that an isoform of pyruvate kinase (M2-PK), a key enzyme in glycolysis, translocates into the nucleus following IL-3 stimulation...
  51. PHYSIOLOGY OF BACTERIA AT LOW TEMPERATURE
    John Ingraham; Fiscal Year: 1980
    ..typhimurium chromosome. The physiological function of the enzyme and the relative role played by it and pyruvate kinase will be studied.
  52. Discovery of Lead Compounds which Modulate Tumor Specific Pyruvate Kinase M2 Acti
    MATTHEW VANDER HEIDEN; Fiscal Year: 2008
    unreadable] DESCRIPTION (provided by applicant): Discovery of lead compounds that modulate tumor specific pyruvate kinase M2 activity Abstract: We propose to discover and optimize selective modulators of human pyruvate kinase M2 (PK-M2)..
  53. 2007 Cellular Osmoregulation: Sensors, Tranducers & Regulators Gordon Research Co
    PAUL YANCEY; Fiscal Year: 2007
    ..In all aspects of the conference, the organizers are working to promote the involvement of women, minorities and people with disabilities. [unreadable] [unreadable] [unreadable]..