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Serine is a natural ligand and allosteric activator of pyruvate kinase M2

Author

Listed:
  • Barbara Chaneton

    (Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK)

  • Petra Hillmann

    (Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK)

  • Liang Zheng

    (Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK)

  • Agnès C. L. Martin

    (Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK)

  • Oliver D. K. Maddocks

    (Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK)

  • Achuthanunni Chokkathukalam

    (Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, B3.09, University of Glasgow, Glasgow G12 8QQ, Scotland, UK)

  • Joseph E. Coyle

    (Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK)

  • Andris Jankevics

    (Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, B3.09, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Groningen Bioinformatics Centre, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen)

  • Finn P. Holding

    (Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK)

  • Karen H. Vousden

    (Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK)

  • Christian Frezza

    (Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK
    Present address: MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 0XZ, UK.)

  • Marc O’Reilly

    (Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK)

  • Eyal Gottlieb

    (Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK)

Abstract

The M2 isoform of pyruvate kinase (PKM2) is a key glycolytic enzyme that is overexpressed in cancer cells; here, serine is shown to bind to and directly activate PKM2, and the resulting reduction in enzyme activity under serine-deprivation conditions is shown to lead to the diversion of glucose-derived carbon to promote serine biosynthesis required for cell proliferation.

Suggested Citation

  • Barbara Chaneton & Petra Hillmann & Liang Zheng & Agnès C. L. Martin & Oliver D. K. Maddocks & Achuthanunni Chokkathukalam & Joseph E. Coyle & Andris Jankevics & Finn P. Holding & Karen H. Vousden & C, 2012. "Serine is a natural ligand and allosteric activator of pyruvate kinase M2," Nature, Nature, vol. 491(7424), pages 458-462, November.
    • Handle: RePEc:nat:nature:v:491:y:2012:i:7424:d:10.1038_nature11540
    DOI: 10.1038/nature11540
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    Cited by:

    1. Rushikesh Patel & Ajay Kumar Raj & Kiran Bharat Lokhande & Mazen A. Almasri & Khalid J. Alzahrani & Asma Saleh Almeslet & K. Venkateswara Swamy & Gargi S. Sarode & Sachin C. Sarode & Shankargouda Pati, 2021. "Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme," IJERPH, MDPI, vol. 18(21), pages 1-11, October.
    2. Rong-Hsuan Wang & Pin-Ru Chen & Yue-Ting Chen & Yi-Chang Chen & Yu-Hsin Chu & Chia-Chen Chien & Po-Chen Chien & Shao-Yun Lo & Zhong-Liang Wang & Min-Chen Tsou & Ssu-Yu Chen & Guang-Shen Chiu & Wen-Lin, 2024. "Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Yinsheng Wu & Lixu Tang & Han Huang & Qi Yu & Bicheng Hu & Gang Wang & Feng Ge & Tailang Yin & Shanshan Li & Xilan Yu, 2023. "Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    4. Wentao Zhao & Cong Ouyang & Liang Zhang & Jinyang Wang & Jiaojiao Zhang & Yan Zhang & Chen Huang & Qiao Xiao & Bin Jiang & Furong Lin & Cixiong Zhang & Mingxia Zhu & Changchuan Xie & Xi Huang & Bingch, 2024. "The proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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