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Author Notes:

To whom correspondence should be addressed: Dept. of Biology, Georgia State University, University Plaza, Atlanta, GA 30303. E-mail: zliu8@gsu.edu.

We are grateful for the comments from Natalie White, Christie Carter, and Yun Huang.


Research Funding:

This work was supported, in whole or in part, by National Institutes of Health Grant CA118113 from NCI.

This work was also supported by the Georgia Cancer Coalition (to Z. R. L.)


  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology

Reciprocal Regulation of Protein Kinase and Pyruvate Kinase Activities of Pyruvate Kinase M2 by Growth Signals


Journal Title:

Journal of Biological Chemistry


Volume 288, Number 22


, Pages 15971-15979

Type of Work:

Article | Final Publisher PDF


Pyruvate kinase isoform M2 (PKM2) is an enzyme-catalyzing conversion of phosphoenolpyruvate to pyruvate in the glycolysis pathway. It was demonstrated that PKM2 interacts with tyrosine phosphopeptide, and the interaction with the tyrosine phosphopeptide affects the pyruvate kinase activity of PKM2. Our experiments suggest that PKM2 is also an active protein kinase (Gao, X., Wang, H., Yang, J. J., Liu, X., and Liu, Z. R. (2012) Mol. Cell 45, 598-609). We report here that growth signals reciprocally regulate the pyruvate kinase and protein kinase activities of PKM2 by different mechanisms. On the one hand, growth signals induce protein tyrosine phosphorylations. The tyrosine-phosphorylated protein(s) regulates the conversion of pyruvate kinase and protein kinase of PKM2 by directly interacting with PKM2. Binding of the tyrosyl-phosphorylated proteins at the fructose 1,6-bisphosphate-binding site converts the tetrameric PKM2 to a dimer. On the other hand, growth stimulations also lead to PKM2 phosphorylation, which consequently regulates the conversion of protein kinase and pyruvate kinase activities. Growth factor stimulations significantly increase the dimer/tetramer PKM2 ratio in cells and consequently activate the protein kinase activity of PKM2. Our study suggests that the conversion between the pyruvate kinase and protein kinase activities of PKM2 may be an important mechanism mediating the effects of growth signals in promoting cell proliferation.

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© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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