title: Lack of Evidence for PKM2 Protein Kinase Activity.
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.
authors: Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Aaron M
authors: AM
authors: Hosios
authors: Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Brian P
authors: BP
authors: Fiske
authors: Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Dan Y
authors: DY
authors: Gui
authors: Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: mvh@mit.edu.
authors: Matthew G
authors: MG
authors: Vander Heiden
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D017353:Gene Deletion; D006019:Glycolysis; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013963:Thyroid Hormones / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000255:Adenosine Triphosphate; D002352:Carrier Proteins; D008565:Membrane Proteins; D010728:Phosphoenolpyruvate; D011494:Protein Kinases; D011770:Pyruvate Kinase; D011994:Recombinant Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins