Pyruvate kinase M2 is a phosphotyrosine-binding protein

Journal Article · Tue Jun 03 04:00:00 EDT 2008 · Nature

DOI:https://doi.org/10.1038/nature06667· OSTI ID:1006614

Christofk, H R; Vander Heiden, M G; Wu, N; Asara, J M; Cantley, L C ^[1]

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1. Harvard-Med

Growth factors stimulate cells to take up excess nutrients and to use them for anabolic processes. The biochemical mechanism by which this is accomplished is not fully understood but it is initiated by phosphorylation of signalling proteins on tyrosine residues. Using a novel proteomic screen for phosphotyrosine-binding proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 (fetal) isoform of pyruvate kinase (PKM2), binds directly and selectively to tyrosine-phosphorylated peptides. We show that binding of phosphotyrosine peptides to PKM2 results in release of the allosteric activator fructose-1,6-bisphosphate, leading to inhibition of PKM2 enzymatic activity. We also provide evidence that this regulation of PKM2 by phosphotyrosine signalling diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Collectively, our results indicate that expression of this phosphotyrosine-binding form of pyruvate kinase is critical for rapid growth in cancer cells.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006614
• Journal Information: Nature, Journal Name: Nature Journal Issue: 03, 2008 Vol. 452
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ENZYMES
GLUCOSE
GLYCOLYSIS
GROWTH FACTORS
HUMAN POPULATIONS
INHIBITION
METABOLITES
NEOPLASMS
NUTRIENTS
PEPTIDES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PRODUCTION
PROTEINS
REGULATIONS
RESIDUES
TYROSINE
USES