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Literature summary for 2.7.1.40 extracted from

  • Ye, J.; Mancuso, A.; Tong, X.; Ward, P.S.; Fan, J.; Rabinowitz, J.D.; Thompson, C.B.
    Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation (2012), Proc. Natl. Acad. Sci. USA, 109, 6904-6909.
    View publication on PubMedView publication on EuropePMC
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Activating Compound

Activating Compound Comment Organism Structure
D-fructose-1,6-bisphosphate isozyme PKM2 requires D-fructose-1,6-bisphosphate to form the active tetramer, but isozyme PKM1 does not Homo sapiens
L-serine an allosteric activator of PKM2, serine-dependent regulation of pyruvate kinase M2 and general control nonderepressible 2 kinase to modulate the flux of glycolytic intermediates in support of cell proliferation Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
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-
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Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein isozyme PKM2can be phosphorylated at Y105 by tyrosine kinases in cancer cells. The PKM2 conformational change caused by phosphorylation leads to FBP release and conversion of the enzyme from the tetramer to the less active dimer form Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
NCI-H1299 cell transfected with PKM-1 or PKM-2 Homo sapiens
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Subunits

Subunits Comment Organism
tetramer
-
 Homo sapiens

Synonyms

Synonyms Comment Organism
PKM1
-
 Homo sapiens
PKM2
-
 Homo sapiens
pyruvate kinase M2
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 Homo sapiens

General Information

General Information Comment Organism
metabolism in the absence of serine, an allosteric activator of PKM2, glycolytic efflux to lactate is significantly reduced in PKM2-expressing cells. This inhibition of PKM2 results in the accumulation of glycolytic intermediates that feed into serine synthesis. the GCN2-ATF4, general control nonderepressible 2 kinase-activating transcription factor 4, pathway collaborates with PKM2-dependent alterations in glycolytic metabolism to coordinate serine synthesis Homo sapiens
physiological function PKM2-expressing cells can maintain mammalian target of rapamycin complex 1 activity and proliferate in serine-depleted medium, but PKM1-expressing cells cannot. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation upon serine depletion, mTOR is a key molecular sensor for nutrient availability and a regulator of cell growth and proliferation. PKM2 confers rsistance to proliferation arrest under serine starvation, tumor cells use serine-dependent regulation of PKM2 and GCN2 to modulate the flux of glycolytic intermediates in support of cell proliferation, overview Homo sapiens