Lack of Evidence for PKM2 Protein Kinase Activity

Mol Cell. 2015 Sep 3;59(5):850-7. doi: 10.1016/j.molcel.2015.07.013. Epub 2015 Aug 20.

Abstract

The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A unique function of PKM2 proposed to be important for the proliferation of some cancer cells involves the direct activity of this enzyme as a protein kinase; however, a detailed biochemical characterization of this activity is lacking. Using [(32)P]-phosphoenolpyruvate (PEP) we examine the direct substrates of PKM2 using recombinant enzyme and in vitro systems where PKM2 is genetically deleted. Labeling of some protein species from [(32)P]-PEP can be observed; however, most were dependent on the presence of ADP, and none were dependent on the presence of PKM2. In addition, we also failed to observe PKM2-dependent transfer of phosphate from ATP directly to protein. These findings argue against a role for PKM2 as a protein kinase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Gene Deletion
  • Glycolysis
  • Humans
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Phosphoenolpyruvate / metabolism
  • Phosphorylation
  • Protein Kinases / deficiency
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Pyruvate Kinase / deficiency
  • Pyruvate Kinase / genetics
  • Pyruvate Kinase / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / deficiency
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Recombinant Proteins
  • Thyroid Hormones
  • Phosphoenolpyruvate
  • Adenosine Triphosphate
  • Protein Kinases
  • Pyruvate Kinase