title: Regulation of pyruvate kinase type M2 by A-Raf: a possible glycolytic stop or go mechanism.
abstract: Recently a link between A-Raf cellular energy homeostasis and synthetic pathways has been suggested through the identification of pyruvate kinase type M2 (M2-PK), a key glycolytic enzyme, as interaction partner of A-Raf In this study, we demonstrated that A-Raf is an important regulator of M2-PK function. In primary mouse fibroblasts, which are characterized by glutamine production and serine degradation, A-Raf induced dimerization and inactivation of M2-PK, thereby reducing conversion rates from glucose to lactate. In immortalized NIH3T3 fibroblasts, showing glutamine degradation and serine production, oncogenic A-Raf increased the highly active tetrameric form of M2-PK and favored glycolytic energy production. High serine levels thus may be responsible for the activation of M2-PK in A-Raf transformed NIH3T3 cells.
authors.affiliation: Institute of Biochemistry and Endocrinology, Veterinary Faculty, Justus-Liebig- University, Giessen, Germany. Sybille.Mazurek@vetmed.uni-giessen.de
authors.forename: Sybille
authors.initials: S
authors.lastname: Mazurek
authors.forename: Hannes C A
authors.initials: HC
authors.lastname: Drexler
authors.forename: Jakob
authors.initials: J
authors.lastname: Troppmair
authors.forename: Erich
authors.initials: E
authors.lastname: Eigenbrodt
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Rapp
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D019281:Dimerization; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D019073:HT29 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D041681:NIH 3T3 Cells; D048491:Proto-Oncogene Proteins A-raf / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
chemical_list: D005973:Glutamine; D012694:Serine; D011770:Pyruvate Kinase; D048491:Proto-Oncogene Proteins A-raf