PGK1, PKM2, KHKC/KHKA acting as protein kinases (WP5433)

Homo sapiens

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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.

Authors

Marcell Levay and Eric Weitz

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

glycolysis pathway kinase mediated signaling pathway

Cell Type Ontology

eukaryotic cell

Participants
Query Drugst.One

Label Type Compact URI Comment
Pyruvate Metabolite hmdb:HMDB0000243
F1-P Metabolite hmdb:HMDB0060467
3-PG Metabolite hmdb:HMDB0000807
1,3-BPG Metabolite hmdb:HMDB0001270
Fructose Metabolite hmdb:HMDB0000660
Lactate Metabolite hmdb:HMDB0000190
Glucose Metabolite hmdb:HMDB0000122
PEP Metabolite hmdb:HMDB0000263
PKM2 GeneProduct uniprot:P14618
KHKC GeneProduct uniprot:P50053
KHKA GeneProduct uniprot:P50053
PGK1 GeneProduct uniprot:P00558
SNAP-23 Protein uniprot:O00161
PAK2 Protein uniprot:Q13177
Bub3 Protein uniprot:O43684
PDHK1 Protein uniprot:Q15118
PRPS1 Protein uniprot:P60891
AKT1S1 Protein uniprot:Q96B36
H3 Protein uniprot:P84243
MLC2 Protein uniprot:P10916
STAT3 Protein uniprot:P40763
Beclin1 Protein uniprot:Q14457
H2AX Protein uniprot:P16104
Bcl2 Protein uniprot:Q9JJV8

References

  1. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Gao X, Wang H, Yang JJ, Liu X, Liu ZR. Mol Cell. 2012 Mar 9;45(5):598–609. PubMed Europe PMC Scholia
  2. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, et al. Cell. 2012 Aug 17;150(4):685–96. PubMed Europe PMC Scholia
  3. PKM2 regulates chromosome segregation and mitosis progression of tumor cells. Jiang Y, Li X, Yang W, Hawke DH, Zheng Y, Xia Y, et al. Mol Cell. 2014 Jan 9;53(1):75–87. PubMed Europe PMC Scholia
  4. PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells. Jiang Y, Wang Y, Wang T, Hawke DH, Zheng Y, Li X, et al. Nat Commun. 2014 Nov 21;5:5566. PubMed Europe PMC Scholia
  5. Pyruvate kinase M2 at a glance. Yang W, Lu Z. J Cell Sci. 2015 May 1;128(9):1655–60. PubMed Europe PMC Scholia
  6. Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1. He CL, Bian YY, Xue Y, Liu ZX, Zhou KQ, Yao CF, et al. Sci Rep. 2016 Feb 15;6:21524. PubMed Europe PMC Scholia
  7. Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis. Li X, Jiang Y, Meisenhelder J, Yang W, Hawke DH, Zheng Y, et al. Mol Cell. 2016 Mar 3;61(5):705–19. PubMed Europe PMC Scholia
  8. A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation. Li X, Qian X, Peng LX, Jiang Y, Hawke DH, Zheng Y, et al. Nat Cell Biol. 2016 May;18(5):561–71. PubMed Europe PMC Scholia
  9. PGK1 is a new member of the protein kinome. Li X, Zheng Y, Lu Z. Cell Cycle. 2016 Jul 17;15(14):1803–4. PubMed Europe PMC Scholia
  10. Fructokinase A acts as a protein kinase to promote nucleotide synthesis. Li X, Qian X, Lu Z. Cell Cycle. 2016 Oct 17;15(20):2689–90. PubMed Europe PMC Scholia
  11. Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2. Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, et al. Cell Res. 2017 Mar;27(3):329–51. PubMed Europe PMC Scholia
  12. Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23. Wei Y, Wang D, Jin F, Bian Z, Li L, Liang H, et al. Nat Commun. 2017 Jan 9;8:14041. PubMed Europe PMC Scholia
  13. Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy. Qian X, Li X, Cai Q, Zhang C, Yu Q, Jiang Y, et al. Mol Cell. 2017 Mar 2;65(5):917-931.e6. PubMed Europe PMC Scholia
  14. Pyruvate kinase M2 phosphorylates H2AX and promotes genomic instability in human tumor cells. Xia L, Qin K, Wang XR, Wang XL, Zhou AW, Chen GQ, et al. Oncotarget. 2017 Nov 17;8(65):109120–34. PubMed Europe PMC Scholia
  15. Pyruvate kinase M2 promotes pancreatic ductal adenocarcinoma invasion and metastasis through phosphorylation and stabilization of PAK2 protein. Cheng TY, Yang YC, Wang HP, Tien YW, Shun CT, Huang HY, et al. Oncogene. 2018 Mar;37(13):1730–42. PubMed Europe PMC Scholia