title: Reciprocal regulation of protein kinase and pyruvate kinase activities of pyruvate kinase M2 by growth signals.
abstract: 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.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Gao
authors.forename: Haizhen
authors.initials: H
authors.lastname: Wang
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Jie
authors.forename: Liangwei
authors.initials: L
authors.lastname: Li
authors.forename: Yinwei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Liu
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011770:Pyruvate Kinase; D011505:Protein-Tyrosine Kinases
keywords: Bioenergetics; Growth Factors; Protein Kinases; Pyruvate Kinase; STAT3