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» Articles » PMID: 22306293

Pyruvate Kinase M2 Regulates Gene Transcription by Acting As a Protein Kinase

Overview
Journal Mol Cell
Publisher Cell Press
Specialty Cell Biology
Date 2012 Feb 7
PMID 22306293
Citations 390
Authors
Xueliang Gao
Haizhen Wang
Jenny J Yang
Xiaowei Liu
Zhi-Ren Liu
Affiliations
Soon will be listed here.
Abstract

Pyruvate kinase isoform M2 (PKM2) is a glycolysis enzyme catalyzing conversion of phosphoenolpyruvate (PEP) to pyruvate by transferring a phosphate from PEP to ADP. We report here that PKM2 localizes to the cell nucleus. The levels of nuclear PKM2 correlate with cell proliferation. PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor. ADP competes with the protein substrate binding, indicating that the substrate may bind to the ADP site of PKM2. Our experiments suggest that PKM2 dimer is an active protein kinase, while the tetramer is an active pyruvate kinase. Expression of a PKM2 mutant that exists as a dimer promotes cell proliferation, indicating that protein kinase activity of PKM2 plays a role in promoting cell proliferation. Our study reveals an important link between metabolism alteration and gene expression during tumor transformation and progression.

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