PGK1, PKM2, KHKC/KHKA acting as protein kinases (Homo sapiens)

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311621057981513121414H2AXFructoseGenomicinstabilityLactateSTAT3MLC2Cell invasionCytokinesisGlucoseMitochondrial pyruvatemetabolismGenetranscriptionBeclin1ExosomesecretionPEPmTOR1activationPRPS1KHKABcl2Mitosis1,3-BPGSNAP-23PKM2ApoptosisF1-PH3 GenetranscriptionKHKCPAK2AKT1S1PDHK1PyruvateBub33-PGDe Novo nucleic acid synthesisPGK1AutophagePPPPPPPPPPPPBeclin1PDHK1Bcl2AKT1S1SNAP-23MLC2Bub3PAK2H3 STAT3H2AXPRPS1


Description

This pathway shows the variable role of metabolic kinases, PGK1, PKM1 and KHKC/KHKA, acting as protein kinases. They are able to phosphorylate and thereby activate second messenger enzymes, which greatly influence cellular functions. This Pathway is based on Figure 1 of the paper "Metabolic Kinases Moonlighting as Protein Kinases" PMID: 29463470.

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Bibliography

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  1. Jiang Y, Wang Y, Wang T, Hawke DH, Zheng Y, Li X, Zhou Q, Majumder S, Bi E, Liu DX, Huang S, Lu Z; ''PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells.''; Nat Commun, 2014 PubMed Europe PMC Scholia
  2. He CL, Bian YY, Xue Y, Liu ZX, Zhou KQ, Yao CF, Lin Y, Zou HF, Luo FX, Qu YY, Zhao JY, Ye ML, Zhao SM, Xu W; ''Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1.''; Sci Rep, 2016 PubMed Europe PMC Scholia
  3. Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, Li C, Yang F, Zeng R, Wei P, Li D, Li W, Yang W; ''Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2.''; Cell Res, 2017 PubMed Europe PMC Scholia
  4. Li X, Qian X, Lu Z; ''Fructokinase A acts as a protein kinase to promote nucleotide synthesis.''; Cell Cycle, 2016 PubMed Europe PMC Scholia
  5. Qian X, Li X, Cai Q, Zhang C, Yu Q, Jiang Y, Lee JH, Hawke D, Wang Y, Xia Y, Zheng Y, Jiang BH, Liu DX, Jiang T, Lu Z; ''Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy.''; Mol Cell, 2017 PubMed Europe PMC Scholia
  6. Cheng TY, Yang YC, Wang HP, Tien YW, Shun CT, Huang HY, Hsiao M, Hua KT; ''Pyruvate kinase M2 promotes pancreatic ductal adenocarcinoma invasion and metastasis through phosphorylation and stabilization of PAK2 protein.''; Oncogene, 2018 PubMed Europe PMC Scholia
  7. Xia L, Qin K, Wang XR, Wang XL, Zhou AW, Chen GQ, Lu Y; ''Pyruvate kinase M2 phosphorylates H2AX and promotes genomic instability in human tumor cells.''; Oncotarget, 2017 PubMed Europe PMC Scholia
  8. Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Alfred Yung WK, Lu Z; ''PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis.''; Cell, 2012 PubMed Europe PMC Scholia
  9. Li X, Qian X, Peng LX, Jiang Y, Hawke DH, Zheng Y, Xia Y, Lee JH, Cote G, Wang H, Wang L, Qian CN, Lu Z; ''A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation.''; Nat Cell Biol, 2016 PubMed Europe PMC Scholia
  10. Jiang Y, Li X, Yang W, Hawke DH, Zheng Y, Xia Y, Aldape K, Wei C, Guo F, Chen Y, Lu Z; ''PKM2 regulates chromosome segregation and mitosis progression of tumor cells.''; Mol Cell, 2014 PubMed Europe PMC Scholia
  11. Li X, Zheng Y, Lu Z; ''PGK1 is a new member of the protein kinome.''; Cell Cycle, 2016 PubMed Europe PMC Scholia
  12. Gao X, Wang H, Yang JJ, Liu X, Liu ZR; ''Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase.''; Mol Cell, 2012 PubMed Europe PMC Scholia
  13. Wei Y, Wang D, Jin F, Bian Z, Li L, Liang H, Li M, Shi L, Pan C, Zhu D, Chen X, Hu G, Liu Y, Zhang CY, Zen K; ''Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23.''; Nat Commun, 2017 PubMed Europe PMC Scholia
  14. Li X, Jiang Y, Meisenhelder J, Yang W, Hawke DH, Zheng Y, Xia Y, Aldape K, He J, Hunter T, Wang L, Lu Z; ''Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis.''; Mol Cell, 2016 PubMed Europe PMC Scholia
  15. Yang W, Lu Z; ''Pyruvate kinase M2 at a glance.''; J Cell Sci, 2015 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
127841view08:17, 23 December 2023Marcell Levay
127840view08:15, 23 December 2023Marcell Levay
127839view07:54, 23 December 2023Marcell LevayModified description
127835view03:18, 23 December 2023EweitzModified description
127817view03:43, 18 December 2023Marcell LevayModified description
127816view03:33, 18 December 2023Marcell LevayModified description
127815view03:27, 18 December 2023Marcell LevayModified title
127814view03:22, 18 December 2023Marcell LevayOntology Term : 'PW:0002666' removed !
127813view03:22, 18 December 2023Marcell LevayOntology Term : 'glycolysis pathway' added !
127812view03:20, 18 December 2023Marcell LevayOntology Term : 'PW:0000001' removed !
127811view03:20, 18 December 2023Marcell LevayOntology Term : 'fructose metabolic pathway' added !
127810view03:17, 18 December 2023Marcell LevayOntology Term : 'kinase mediated signaling pathway' added !
127809view03:12, 18 December 2023Marcell LevayOntology Term : 'eukaryotic cell' added !
127808view03:10, 18 December 2023Marcell LevayOntology Term : 'Pathway Ontology' added !
127807view03:00, 18 December 2023Marcell LevayNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1,3-BPGMetaboliteHMDB0001270 (HMDB)
3-PGMetaboliteHMDB0000807 (HMDB)
AKT1S1ProteinQ96B36 (Uniprot-TrEMBL)
ApoptosisPathwayWP2507 (WikiPathways)
Autophage Pathway
Bcl2ProteinQ9JJV8 (Uniprot-TrEMBL)
Beclin1ProteinQ14457 (Uniprot-TrEMBL)
Bub3ProteinO43684 (Uniprot-TrEMBL)
Cell invasion Pathway
CytokinesisPathway
De Novo nucleic acid synthesisPathway
Exosome secretionPathway
F1-PMetaboliteHMDB0060467 (HMDB)
FructoseMetaboliteHMDB0000660 (HMDB)
Gene transcriptionPathway
Genomic instabilityPathway
GlucoseMetaboliteHMDB0000122 (HMDB)
H2AXProteinP16104 (Uniprot-TrEMBL)
H3 ProteinP84243 (Uniprot-TrEMBL)
KHKAGeneProductP50053 (Uniprot-TrEMBL)
KHKCGeneProductP50053 (Uniprot-TrEMBL)
Lactate MetaboliteHMDB0000190 (HMDB)
MLC2ProteinP10916 (Uniprot-TrEMBL)
Mitochondrial
pyruvate
metabolism
Pathway
MitosisPathway
PAK2ProteinQ13177 (Uniprot-TrEMBL)
PDHK1ProteinQ15118 (Uniprot-TrEMBL)
PEPMetaboliteHMDB0000263 (HMDB)
PGK1GeneProductP00558 (Uniprot-TrEMBL)
PKM2GeneProductP14618 (Uniprot-TrEMBL)
PRPS1ProteinP60891 (Uniprot-TrEMBL)
PyruvateMetaboliteHMDB0000243 (HMDB)
SNAP-23ProteinO00161 (Uniprot-TrEMBL)
STAT3ProteinP40763 (Uniprot-TrEMBL)
mTOR1 activationPathway

Annotated Interactions

No annotated interactions

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