Table 2.
PKM2 interacting protein & Interaction site & Biological Function & References
| PKM2 interacting protein | ||||
|---|---|---|---|---|
| Protein | Site | Biological function | References | |
| 1 | A-Raf | Phosphorylation modification, unknown site | Regulate the composition ratio between PKM2 dimer and tetramer, and then regulate the glucose metabolism of tumor cells | Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells |
| 2 | AKT1S1 | PKM2 phosphorylates AKT1S1 at serine202 and serine203 (S202/203) | Activation of ATP-dependent mTOR signaling pathways | Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1 |
| 3 | BCL2 | PKM2 phosphorylates Bcl2 threonine (T-69) (HSP90 stabilizes PKM2-BCL2 complex) | The phosphorylation prevents the binding of Cul3-based E3 ligase to Bcl2 and subsequent degradation of Bcl2, thereby inhibiting oxidative stress-induced apoptosis | Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2 |
| 4 | BCR-ABL | Phosphorylation modification, unknown site | Fusion of breakpoint cluster region and ABL1, disruption of the formation of the tetrameric form of PKM2 | Association of the src gene product of Rous sarcoma virus with cytoskeletal structures of chicken embryo fibroblasts. |
| 5 | β-catenin | The k433 site of PKM2 is a key site for binding to y333 phosphorylated β-catenin | PKM2-β-catenin (Y333p) can promote the proliferation and malignant transformation of tumor cells | Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation |
| 6 | CD44 | Phosphorylation modification, unknown site | PKM2 binds to CD44 to inhibit phosphorylation of serine at a certain position in PKM2, thereby promoting aerobic glycolysis and promoting glucose metabolism to biosynthesis | Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth |
| 7 | CARM1 | Methylated PKM2 exon 10, the specific location is unknown | PKM2 methylated by Carm1 can promote aerobic glycolysis and malignant transformation of tumors | PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis |
| 8 | ERK1/2 | After binding to SAICAR, PKM2 phosphorylates ERK1 at t202, y204 sites and ERK2 to t202 siteAnd ERK2 phosphorylates PKM2 at s37 site | Erk and PKM2 together form a positive feedback activation loop that activates the ERK/MAPK pathway Phosphorylated PKM2 can increase its nuclear localization and promote cell proliferation | SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells |
| 9 | ETV6–NTRK3 | Phosphorylation modification, unknown site | Fusion of Est variant 6 and neurotrophic tyrosine kinase receptor, disruption of the formation of the tetrameric form of PKM2 | Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein |
| 10 | HERC-1 | Binding to PKM2 at AA 406–531 | GTP producer for guanine nucleotide exchange factor RLD1 | Interaction between HERC1 and M2-type pyruvate kinase |
| 11 | HIF-1a | Binding to PKM2 | Augmentation of the trans-activating activity of HIF-1a | Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1 |
| 12 | HCV NS5B | Binding to PKM2 | Indications for a role of PKM2 in HCV RNA synthesis | Hepatitis C virus RNA functionally sequesters miR-122 |
| 13 | HPV-16 E7 | Binding to PKM2 | Dimerization and inhibition of PKM2 | Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutami- nolysis: role of pyruvate kinase type M2 and the glycolytic-enzyme complex. |
| 14 | HSC70 | Acetylation of Lys305 site for PKM2 | By inhibiting the biological effects of PKM2 by acetylation of the PKM2 Lys305 site, it mediates the binding of PKM2 to HSC70 and attenuates the degradation of PKM2 via the lysosomal pathway | Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone—mediated autophagy and promotes tumor growth |
| 15 | HSP70 | Acetylation modification, unknown site | HSP70 can acetylate PKM2, which mediates intracellular localization of lysosomes, thereby maintaining intracellular homeostasis | Proviral insertion in murine lymphomas 2 (PIM2)oncogene Dual roles of PKM2 in cancer metabolism |
| 16 | H3 | PKM2 can phosphorylate histone H3 T11 | Phosphorylated histones can promote the G1-S phase transition of tumor cells, phosphorylation of stat3 can promote the production of cyclinD, phosphorylation of MLC2 can enhance the activity of MAPK pathway, and phosphorylated Bub3 can enhance the activity of EGFR pathway | Pyruvate kinase M2 at a glance |
| 17 | STAT3 | PKM2 can phosphorylate stat3 Y705 | ||
| 18 | MLC2 | PKM2 can phosphorylate MLC2 Y118 | ||
| 19 | Bub3 | PKM2 can phosphorylate Bub3 Y27 site | ||
| 20 | FLT3 | Phosphorylation modification, unknown site | Fms-related tyrosine kinase, internal tandem duplication (ITD) mutant, disruption of the formation of the tetrameric form of PKM2 | Association of the src gene product of Rous sarcoma virus with cytoskeletal structures of chicken embryo fibroblasts. |
| 21 | FGFR1 | FGFR1 can phosphorylates PKM2 atTyr 83, Tyr105, Tyr148, Tyr175, Tyr370, Tyr390 site | Inhibits the biological activity of PKM2 which coule regulate the glucose metabolism in tumor cells | TRIM35 Interacts with pyruvate kinase isoform M2 to suppress the Warburg effect and tumorigenicity in hepatocellular carcinoma |
| 22 | JAK2 | Phosphorylation modification, unknown site | Disruption of the formation of the tetrameric form of PKM2 | Association of the src gene product of Rous sarcoma virus with cytoskeletal structures of chicken embryo fibroblasts. |
| 23 | JNK1 | JNK1 phosphorylates PKM2 at Thr365 site | Inhibits the biological activity of PKM2 which coule regulate the glucose metabolism in tumor cells, and the nuclear transfer of PKM2 is inhibited, which in turn inhibits the biological role of PKM2 in the nucleus | PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation |
| 24 | GSK-3β | GSK-3β phosphorylation of PKM2 Thr-328 (HSP90 stable PKM2-GSK3β complex) | Thr-328 phosphorylation is essential for maintaining PKM2 stability and its biological function in regulating glycolysis, mitochondrial respiration, proliferation and apoptosis | HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma |
| 25 | P53 | Phosphorylation modification, unknown site | PKM2-P53 can promote the proliferation and malignant transformation of tumor cells | Dual roles of PKM2 in cancer metabolism |
| 26 | p300 | PKM2 could be acetylated by p300 at K433 site | PKM2 K433 acetylation converts cell proliferation and cytoplasmic metabolic kinase to nuclear protein kinase activity | Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization |
| 27 | PAK2 | PKM2 directly phosphorylates PAK2 (HSP90-stabilized PKM2-PAK2 complex) on Ser20, Ser141 (phosphorylated but weakly acting) and ser192/197 (action site) | Phosphorylation of serine 192/197 mediated by pkm2 in PDAC cells is critical for maintaining PAK2 levels phosphorylation of ser192/197 promotes the association of HSP90 with PAK2, thereby preventing ubiquitin and protease degradation of PAK2 | Pyruvate kinase M2 promotes pancreatic ductal adenocarcinoma invasion and metastasis through phosphorylation and stabilization of PAK2 protein |
| 28 | PANK-4 | Binding to PKM2 | Reduction of the activity of the tetrameric form | Dual roles of PKM2 in cancer metabolism |
| 29 | Parkin | Parkin promotes ubiquitination of Lys186 and Lys206 sites in PKM2 | Parkin inhibits the biological activity of PKM2 and regulates glucose metabolism by promoting ubiquitination of Lys186 and Lys206 sites of PKM2 | Parkin regulates the activity of pyruvate kinase M2 |
| 30 | PCAF | Acetylates modification, unknown site | Reduction of the activity of the tetrameric form | Dual roles of PKM2 in cancer metabolism |
| 31 | PHD3 | PDH3 can hydroxylate the Pro403 and Pro408 sites of PKM2 | PKM2 binds to PDH3, and modified PKM2 is more susceptible to HIF-1α binding and forms an activation loop that promotes anaerobic glycolysis and metabolic recombination | Pyruvate kinase M2 is a PHD3—stimulated coactivator for hypoxia—inducible factor 1 |
| 32 | PKC ♁ | Phosphorylation modification, unknown site | Hypothesis: regulation of stability or degradation of M2-PK | Dual roles of PKM2 in cancer metabolism |
| 33 | PIAS3 | Binding to PKM2 at AA 1–348 | Sumoylation of PKM2 and nuclear translocation of PKM2 | The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2 |
| 34 | PML | Binding to PKM2 | Reduction of the activity of the tetrameric form | Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein |
| 35 | PIM2 | PIM2 can phosphorylate PKM2 at Thr454 site | PIM2 phosphorylates the PKM2 Thr454 site, mediates PKM2-dependent anaerobic glycolysis, and maintains mitochondrial function in tumor cells | Proviral insertion in murine lymphomas 2 (PIM2)oncogene phosphorylates pyruvate kinase M2 (PKM2) and promotes glycolysisin cancer cells |
| 36 | PTP1B | PTP1B phosphorylates the Tyr105 and Tyr148 site of PKM2 | PTP1B inhibits the biological activity of PKM2 by phosphorylating the Tyr105 and Tyr148 site of PKM2 | Protein tyrosine phosphatase 1B regulates pyruvate kinase M2 tyrosine phosphorylation |
| 37 | PRMT4 | PRMT4 methylates specifically the dimeric form of PKM2 at Arg445/447/455 residues in the C domain | Allosteric activators inhibit PKM2 tetramerization form thought PKM2 methylation | Posttranslational modifications of pyruvate kinase M2: tweaks that benefit cancer |
| 38 | MG | MG can glycosylate the Arg399 site of PKM2 | MG can glycosylate the Arg399 site of PKM2, the result of which can change the spatial configuration of PKM2 | Molecular association of glucose-6-phosphate isomerase and pyruvate kinase M2 with glyceraldehyde-3-phosphate dehy-drogenase in cancer cell |
| 39 | Oct No. 4 | Binding to PKM2 at AA 307–531 | Augmentation of the trans-activating activity of Oct 4 | Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription. |
| 40 | Opa | Binding to PKM2 at AA 367–531 | Outer membrane proteins involved in gonococcal adhesion to and invasion of human epithelial cells creation of a microenvironment of high pyruvate concentration | Posttranslational modifications of pyruvate kinase M2: tweaks that benefit cancer |
| 41 | O_GlcNAcylation | O-GlcNAcylation can block the Thr 405 and Ser 406 sites of PKM2 | Decreased the stability of the tetrameric form of PKM2 to enhance aerobic glycolysis (Warburg effect) | O-GlcNAcylation destabilizes the active tetrameric PKM2 to promote the Warburg effect |
| 42 | SAICAR | Mutation of the G415 site of PKM2 to R will not bind to SAICAR | PKM2 binds to SAICAR, and mutations at the PKM2 G415 site prevent PKM2 from binding to SAICAR | SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells |
| 43 | SIRT-6 | Deacetylation modification, the site is unknown | SIRT6 mediates the deacetylation of PKM2, and the results mediate the nuclear localization of PKM2 | SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions |
| 44 | SOCS-3 | Binding to PKM2 | Reduction of ATP production and influence of dendritic cell immune response | Posttranslational modifications of pyruvate kinase M2: tweaks that benefit cancer |
| 45 | TEM8 | Binding to PKM2 | Stimulation of angiogenesis by binding of Tumor M2-PK released from tumors | Dual roles of PKM2 in cancer metabolism |
| 46 | TEPP-46 | Binding to PKM2 | TEPP-46 and FBP, the allosteric activators that induce PKM2 tetramerization | Posttranslational modifications of pyruvate kinase M2: tweaks that benefit |
| 47 | TRIM35 | MiR-4417 targets TRIM35 and regulates PKM2 Y105 phosphorylation | Promote proliferation and suppress apoptosis, PKM2 Y105 phosphorylation to promote HCC growth | MiR-4417 targets tripartite Motif-containing 35 (TRIM35) and regulates pyruvate kinase muscle 2 (PKM2) phosphorylation to promote proliferation and suppress apoptosis in hepatocellular carcinoma cells |