Lack of Evidence for PKM2 Protein Kinase Activity
Author(s)Hosios, Aaron Marc; Fiske, Brian Prescott; Gui, Dan Yi; Vander Heiden, Matthew G.
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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 [32P]-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 [32P]-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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology
Hosios, Aaron M. et al. “Lack of Evidence for PKM2 Protein Kinase Activity.” Molecular Cell 59.5 (2015): 850–857.
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