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  • Title: Regulation of pyruvate kinase type M2 by A-Raf: a possible glycolytic stop or go mechanism.
    Author: Mazurek S, Drexler HC, Troppmair J, Eigenbrodt E, Rapp UR.
    Journal: Anticancer Res; 2007; 27(6B):3963-71. PubMed ID: 18225557.
    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.
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