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Literature summary for 2.7.1.40 extracted from

  • Mazurek, S.
    Pyruvate kinase M2: A key enzyme of the tumor metabolome and its medical relevance (2012), Biomed. Res., 23, 133-142.
No PubMed abstract available

Activating Compound

Activating Compound Comment Organism Structure
D-fructose 1,6-bisphosphate induces an association of two inactive dimers to the active tetrameric form Homo sapiens
D-fructose 1,6-bisphosphate induces an association of two inactive dimers to the active tetrameric form. M2-PK showing ProTalpha kinase activity is a trimeric association and possesses no observable pyruvate kinase activity. This association can be shifted by fructose 1,6-P2 to the tetrameric form which results in a reduction of ProTalpha-kinase activity Mus musculus

Application

Application Comment Organism
diagnostics M2-PK in stool is a screening marker for colorectal cancer. M2-PK in plasma is a marker for follow-up studies during tumor therapy Homo sapiens
drug development M2-PK is a potential target for tumor therapy, detailed overview Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information IgE receptor FcepsilonRI rapid phosphorylation of tyrosine residues in M2-PK leads to its inhibition and initiation of mast cell degranulation Homo sapiens
suppressor of cytokine signaling 3 in dendritic cells the interaction of M2-PK with suppressor of cytokine signaling 3, SOCS3, induces a decrease of M2-PK activity and ATP production as well as an impairment of dendritic cell-based immunotherapy against tumors Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Homo sapiens 5829
-
additional information nuclear translocation of M2-PK by the somatostatin analogue TT232, H2O2 or UV light Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + prothymosin alpha Mus musculus in normal murine lymphocytes and in tumor cells M2-PK phosphorylates prothymosin alpha on a threonine ADP + phospho-prothymosin alpha
-
?
ATP + pyruvate Mus musculus
-
ADP + phosphoenolpyruvate
-
r
ATP + pyruvate Homo sapiens
-
ADP + phosphoenolpyruvate
-
r
additional information Homo sapiens nuclear M2-PK participates in the phosphorylation of the epsilon-amino group of histone 1 by direct phosphate transfer from PEP without requiring ATP. M2-PK directly inters with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein IgE receptor FcepsilonRI rapid phosphorylation of tyrosine residues in M2-PK leads to its inhibition and initiation of mast cell degranulation Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
adipocyte expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-
embryo expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-
Henles loop expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-
lung expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-
lymphocyte
-
Mus musculus
-
additional information M2-type pyruvate kinase isoenzyme is expressed in different differentiated cells and tissues as well as in all proliferating cells Mus musculus
-
additional information M2-type pyruvate kinase isoenzyme is expressed in different differentiated cells and tissues as well as in all proliferating cells. Increase of tumor M2-PK in plasma of patients with renal cell carcinoma, melanoma, lung, breast, cervical, ovarian, oesopharyngeal, gastric, pancreatic and colorectal cancer as well as in pleural fluid of patients with chest malignancies which correlates with tumor stages Homo sapiens
-
pancreatic islet expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-
renal medulla expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-
renal tubule distal, expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-
retina expression of M2-type pyruvate kinase isoenzyme Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + prothymosin alpha in normal murine lymphocytes and in tumor cells M2-PK phosphorylates prothymosin alpha on a threonine Mus musculus ADP + phospho-prothymosin alpha
-
?
ATP + prothymosin alpha ProTalpha kinase activity Mus musculus ADP + phospho-prothymosin alpha
-
?
ATP + pyruvate
-
Mus musculus ADP + phosphoenolpyruvate
-
r
ATP + pyruvate
-
Homo sapiens ADP + phosphoenolpyruvate
-
r
additional information nuclear M2-PK participates in the phosphorylation of the epsilon-amino group of histone 1 by direct phosphate transfer from PEP without requiring ATP. M2-PK directly inters with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
dimer nearly inactive dimeric form Mus musculus
dimer nearly inactive dimeric form Homo sapiens
More in tumors, the dimeric form of M2-PK is predominant due to direct interaction with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides Homo sapiens
tetramer highly active tetrameric form Mus musculus
tetramer highly active tetrameric form Homo sapiens
trimer M2-PK showing ProTalpha kinase activity is a trimeric association and possesses no observable pyruvate kinase activity Mus musculus

Synonyms

Synonyms Comment Organism
M2-PK
-
Mus musculus
M2-PK
-
Homo sapiens
PKM2
-
Mus musculus
PKM2
-
Homo sapiens
pyruvate kinase M2
-
Mus musculus
pyruvate kinase M2
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ADP
-
Mus musculus
ADP
-
Homo sapiens
ATP
-
Mus musculus
ATP
-
Homo sapiens

Expression

Organism Comment Expression
Homo sapiens HIF-1alpha induces an increased transcription of the pyruvate kinase M gene.. Induction of M2-PK expression by hypermethylated secreted frizzled related protein and mutated adenomatous polyposis coli protein, APC, overview up

General Information

General Information Comment Organism
malfunction missense mutations of M2-PK are described in the lymphocytes of an Indian Bloom syndrome patient. Inhibition of M2-PK isdirectly linked with the initiation of mast cell degranulation Homo sapiens
additional information expression of M2-PK is under the control of nutrients, insulin, different transcription factors such as SP1, SP3, HIF-1alpha, as well as c-myc, the zonula occludens protein 2 (ZO-2), Ras and microRNA 133a and 133b Homo sapiens
physiological function pyruvate kinase is a glycolytic enzyme catalyzing the ATP regenerating dephosphorylation of phosphoenolpyruvate to pyruvate. Pyruvate kinase is responsible for net ATP production within the glycolytic sequence. Besides its role as glycolytic enzyme M2-PK may also function as protein kinase Mus musculus
physiological function pyruvate kinase is a glycolytic enzyme catalyzing the ATP regenerating dephosphorylation of phosphoenolpyruvate to pyruvate. Pyruvate kinase is responsible for net ATP production within the glycolytic sequence. Besides its role as glycolytic enzyme M2-PK may also function as protein kinase. In tumor metabolism the quaternary structure of M2-PK (tetramer:dimer ratio) determines whether glucose is used for glycolytic energy regeneration (highly active tetrameric form, Warburg effect) or synthesis of cell building blocks (nearly inactive dimeric form) which are both prerequisites for cells with a high proliferation rate. In tumor cells the nearly inactive dimeric form of M2-PK is predominant due to direct interactions with different oncoproteins. Besides its key functions in tumor metabolism, M2-PK may also react as protein kinase as well as co activator of transcription factors. The mTOR/HIF-1a/c-myc/M2-PK cascade may be one explanation for the increased aerobic glycolysis in tumor cells first described by Otto Warburg, overview. Nuclear translocation of M2-PK by the somatostatin analogue TT232, H2O2 or UV light are linked to the induction of caspase independent apoptosis. M2-PK binds to the mast cell IgE receptor FcepsilonRI and plays a crucial role in responses to allergens Homo sapiens