Regulation of Pyruvate Kinase Type M2 by A-Raf: A Possible Glycolytic Stop or Go Mechanism

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 f...

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Bibliographic Details
Published in:Anticancer research 2007-11, Vol.27 (6B), p.3963-3971
Main Authors: MAZUREK, Sybille, DREXLER, Hannes C. A, TROPPMAIR, Jakob, EIGENBRODT, Erich, RAPP, Ulf R
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Transformation, Neoplastic - metabolism
Dimerization
Fibroblasts - enzymology
Fibroblasts - pathology
Glutamine - metabolism
Glycolysis
HT29 Cells
Humans
Immunoprecipitation
Medical sciences
Mice
NIH 3T3 Cells
Proto-Oncogene Proteins A-raf - metabolism
Pyruvate Kinase - metabolism
Serine - metabolism
Tumors
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Summary: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.
ISSN:0250-7005
1791-7530