Lack of Evidence for PKM2 Protein Kinase Activity

Autor: Aaron M. Hosios, Brian P. Fiske, Matthew G. Vander Heiden, Dan Y. Gui
Přispěvatelé: Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Hosios, Aaron Marc, Fiske, Brian Prescott, Gui, Dan Yi, Vander Heiden, Matthew G.
Rok vydání: 2015
Předmět:
Zdroj: PMC
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2015.07.013
Popis: 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.
Howard Hughes Medical Institute (International Student Research Fellowship)
Vertex Pharmaceuticals Incorporated. Vertex Scholars Program
Massachusetts Institute of Technology. Department of Biology (Grant T32GM007287)
David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Student Fellowship)
National Cancer Institute (U.S.) (Grants R01CA168653 and P30CA14051)
Burroughs Wellcome Fund
Databáze: OpenAIRE