Affinage

PKM

Pyruvate kinase PKM · UniProt P14618

Round 2 corrected
Length
531 aa
Mass
57.9 kDa
Annotated
2026-04-28
130 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PKM encodes pyruvate kinase M, a glycolytic enzyme whose PKM2 splice isoform functions as a metabolic switch regulated by oligomeric state: the active tetramer catalyzes pyruvate production, whereas the dimer translocates to the nucleus to serve as a transcriptional coactivator for HIF-1α, β-catenin, and STAT3 and to phosphorylate histone H3 at T11 and the checkpoint protein Bub3 at Y207 using PEP as phosphate donor, thereby coupling glucose metabolism to gene expression, cell-cycle progression, and mitotic fidelity (PMID:18337815, PMID:22056988, PMID:22901803, PMID:24316223). Tetramer–dimer interconversion is governed by allosteric activators (fructose-1,6-bisphosphate, serine), phosphotyrosine peptide binding, ROS-mediated C358 oxidation, and an array of post-translational modifications—including Y105 phosphorylation by FGFR1, S37 phosphorylation by ERK2 triggering PIN1-dependent nuclear import, K305 acetylation directing chaperone-mediated autophagy, C31 palmitoylation, K62 lactylation, K33-linked polyubiquitination by March2, and prolyl hydroxylation by PHD3—that collectively tune the balance between glycolysis and biosynthetic/transcriptional outputs (PMID:19920251, PMID:23178880, PMID:22052977, PMID:21620138, PMID:22096030, PMID:39665133, PMID:36439872, PMID:40079144). Nuclear PKM2 also binds RNA G-quadruplex structures in pre-mRNAs, competing with repressive RNA-binding proteins to promote epithelial-to-mesenchymal transition, and interacts with ribosomes in a PARylation-dependent manner to modulate translation (PMID:39153475, PMID:37224531). In immune cells, PKM2 promotes NLRP3/AIM2 inflammasome activation via EIF2AK2 phosphorylation in macrophages and enhances STAT3-dependent Th17 differentiation, with myeloid- or T cell-specific deletion protecting against sepsis, stroke-related neuroinflammation, and autoimmune encephalomyelitis (PMID:27779186, PMID:32697823, PMID:34529778).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2008 High

    The question of how growth factor signaling inhibits pyruvate kinase activity was answered by demonstrating that PKM2 uniquely binds tyrosine-phosphorylated peptides, which release FBP and suppress enzymatic activity, establishing the phosphotyrosine-sensing mechanism that diverts glucose to biosynthesis.

    Evidence Proteomic screen for phosphotyrosine-binding proteins with in vitro binding and metabolic flux analysis

    PMID:18337815

    Open questions at the time
    • Identity of endogenous phosphotyrosine ligands in vivo not fully catalogued
    • Structural basis of FBP release upon phosphotyrosine binding not resolved
  2. 2009 High

    The splicing regulation determining PKM2 versus PKM1 expression was elucidated: c-Myc-driven hnRNP proteins (PTB, hnRNPA1/A2) repress exon 9 inclusion to enforce the PKM2 isoform in cancer, while oncogenic FGFR1 was shown to directly phosphorylate PKM2 at Y105 to disrupt tetramerization, establishing two converging mechanisms—transcriptional splicing control and post-translational inhibition—that sustain the Warburg effect.

    Evidence RNA-IP and splicing assays for hnRNP regulation; in vitro kinase assays with Y105F mutagenesis and xenograft validation for FGFR1 phosphorylation

    PMID:19920251 PMID:20010808

    Open questions at the time
    • Whether additional kinases besides FGFR1 phosphorylate Y105 in specific tumor contexts
    • Quantitative contribution of each hnRNP to PKM2/PKM1 ratio in different tissues
  3. 2010 High

    The discovery that PEP directly phosphorylates PGAM1 at catalytic H11 in PKM2-expressing cells revealed an alternative glycolytic phosphotransfer route, establishing PKM2 as a histidine kinase using PEP rather than ATP.

    Evidence Mass spectrometry identification of phospho-His11-PGAM1 with isotope-labeled metabolic flux assays

    PMID:20847263

    Open questions at the time
    • Whether PKM2 directly catalyzes this transfer or facilitates non-enzymatic PEP phosphorylation was debated until 2021
  4. 2011 High

    Multiple studies collectively established that PKM2 functions beyond glycolysis as a nuclear transcriptional coactivator: it binds HIF-1α (enhanced by PHD3-mediated prolyl hydroxylation at P403/P408), interacts with β-catenin at K433 to drive cyclin D1 expression, and is subject to ROS-mediated C358 oxidation that diverts flux to the pentose phosphate pathway and serine allosteric activation that tunes activity to amino acid availability.

    Evidence Co-IP, MS-verified hydroxylation, ChIP, reporter assays, and mutagenesis for HIF-1α and β-catenin interactions; in vitro oxidation and C358S mutagenesis with xenograft models; direct serine binding and enzymatic assays

    PMID:21620138 PMID:22052977 PMID:22056988 PMID:23064226

    Open questions at the time
    • Nuclear import mechanism for PKM2 to reach HIF-1α not yet detailed at this stage
    • Relative contributions of HIF-1α versus β-catenin coactivation in different tumor types
  5. 2012 High

    The nuclear import pathway was resolved: ERK2 phosphorylates PKM2 at S37, PIN1 isomerizes pS37-PKM2 for importin α5 binding and nuclear entry, where PKM2 phosphorylates histone H3T11 (using PEP) to activate CCND1/MYC transcription; PKM2 was also reported to phosphorylate STAT3-Y705, though this protein kinase activity was later contested.

    Evidence In vitro kinase assays, S37A nuclear translocation-deficient mutant, ChIP for H3T11p, recombinant histone H3 phosphorylation, in vivo brain tumor models; [32P]-PEP STAT3 phosphorylation assay

    PMID:22306293 PMID:22901803 PMID:23178880

    Open questions at the time
    • The general protein kinase activity of PKM2 was challenged by Hosios et al. 2015, creating unresolved controversy around non-histone substrates
    • Quantitative contribution of H3T11 phosphorylation versus other chromatin marks not determined
  6. 2013 High

    PKM2's nuclear functions were extended to mitosis: JMJD5 binds the PKM2 intersubunit interface to block tetramerization and promote nuclear HIF-1α coactivation, while PKM2 phosphorylates the spindle checkpoint protein Bub3 at Y207 to enable correct kinetochore-microtubule attachment and chromosome segregation.

    Evidence Co-IP with tetramerization assays for JMJD5; in vitro kinase assay, Y207 mutagenesis, and kinetochore localization for Bub3

    PMID:24316223 PMID:24344305

    Open questions at the time
    • Whether Bub3-Y207 phosphorylation by PKM2 is subject to the same protein kinase controversy raised by Hosios et al.
    • Structural basis of JMJD5 docking at the intersubunit interface
  7. 2014 High

    Aurora B phosphorylation of PKM2 at T45 was shown to direct PKM2 to the contractile ring during cytokinesis, where it phosphorylates MLC2 at Y118 to prime ROCK2-dependent S15 phosphorylation, establishing a mitotic function for PKM2 beyond the spindle checkpoint.

    Evidence In vitro kinase assays, T45/Y118 mutagenesis, subcellular localization, and cytokinesis assays with in vivo brain tumor validation

    PMID:25412762

    Open questions at the time
    • Relationship between PKM2 protein kinase activity at MLC2 and the Hosios et al. challenge
    • Whether PKM1 has any compensatory role during cytokinesis
  8. 2015 High

    A rigorous reconstitution study challenged PKM2's proposed direct protein kinase activity, finding that [32P]-PEP-dependent phospholabeling depended on ADP contamination rather than direct PKM2 catalysis, creating a major unresolved controversy regarding histone H3, STAT3, Bub3, and MLC2 phosphorylation claims.

    Evidence In vitro [32P]-PEP assays with recombinant PKM2 and PKM2-null cell extracts

    PMID:26300261

    Open questions at the time
    • The contradiction with multiple independent labs reporting direct PKM2-dependent phosphorylation has not been fully resolved
    • Whether specific substrates (e.g., PGAM1-H11) are exceptions to the negative finding
  9. 2016 High

    PKM2 was established as a critical immunometabolic regulator: it promotes NLRP3/AIM2 inflammasome activation via EIF2AK2 phosphorylation in macrophages, with myeloid-specific PKM2 deletion protecting against lethal sepsis; separately, a Cdc25A-PKM2-β-catenin positive feedback loop was identified driving glycolytic gene expression.

    Evidence Myeloid-specific conditional KO with in vivo sepsis/endotoxemia models; in vitro phosphatase assay of Cdc25A on PKM2-pS37 with mutagenesis

    PMID:27485204 PMID:27779186

    Open questions at the time
    • Whether PKM2's inflammasome role is kinase-dependent or metabolite-dependent
    • Tissue-specific differences in the Cdc25A feedback loop
  10. 2020 High

    T cell-specific and cardiomyocyte-specific knockouts revealed non-metabolic roles: nuclear PKM2 enhances STAT3 phosphorylation to drive Th17 differentiation and autoimmunity, while cardiomyocyte PKM2 regulates cell-cycle re-entry via β-catenin signaling with therapeutic implications for myocardial infarction repair.

    Evidence Conditional KO mice with EAE model for Th17; cardiomyocyte KO with mRNA rescue after MI

    PMID:32078387 PMID:32697823

    Open questions at the time
    • Mechanism by which PKM2 activates STAT3 independent of its contested protein kinase activity
    • Long-term effects of PKM2 mRNA delivery on cardiomyocyte proliferation and arrhythmia risk
  11. 2022 Medium

    Novel post-translational modifications were identified as oligomeric-state regulators: K62 lactylation stabilizes tetramers and suppresses the Warburg effect in macrophages; C31 palmitoylation by zDHHC13 disrupts tetramerization in endothelial cells; and K33-linked polyubiquitination by March2 promotes tetramer formation in vascular smooth muscle cells, linking PKM2 regulation to cardiovascular pathology.

    Evidence Lactylation proteomics with K62 mutagenesis; palmitoyl-proteomics with C31S mutant and AAV rescue in ApoE−/− mice; ubiquitination assays with K33-linkage specificity and smooth muscle cell-specific KO

    PMID:36439872 PMID:39665133 PMID:40079144

    Open questions at the time
    • Interplay among lactylation, palmitoylation, and ubiquitination on the same PKM2 molecule not studied
    • Whether K33-linked ubiquitination occurs broadly or is tissue-restricted
  12. 2023 High

    Degradation pathways for PKM2 were clarified: PHGDH protects PKM2 from PCAF-mediated K305 acetylation and CMA degradation while promoting p300-mediated K433 acetylation for nuclear entry; JMJD4 hydroxylates K66 to trigger Hsp70-mediated CMA, with cardiomyocyte Jmjd4 loss causing dilated cardiomyopathy from PKM2 accumulation, rescuable by TEPP-46.

    Evidence Co-IP with writer identification (PCAF, p300), autophagy assays, vascular aging model; MS-verified K66 hydroxylation, cardiomyocyte-specific Jmjd4 KO with pharmacologic rescue

    PMID:36899022 PMID:37066795

    Open questions at the time
    • How K305 acetylation and K66 hydroxylation CMA pathways are coordinated or prioritized
    • Whether JMJD4-PKM2 axis operates outside cardiomyocytes
  13. 2024 High

    Nuclear PKM2 was revealed as a non-canonical RNA-binding protein that specifically recognizes RNA G-quadruplex structures in pre-mRNAs, competing with repressive RBPs like HNRNPF to promote expression of an 'rG4ome' gene set driving EMT and invasion, while ribosome-associated PKM was shown to cause PARylation-dependent translational stalling near lysine/glutamate codons.

    Evidence eCLIP-seq for nuclear PKM2-RNA crosslinks with rG4 structure probing and HNRNPF competition; polysome fractionation proteomics with ribosome footprinting and ADP titration

    PMID:37224531 PMID:39153475

    Open questions at the time
    • Whether rG4 binding requires the dimeric conformation specifically
    • Functional overlap between PKM2's translational stalling role and its RNA G-quadruplex binding
  14. 2025 Medium

    PINK1 was identified as a kinase that phosphorylates PKM2 at S127 to stabilize tetramers and prevent nuclear translocation, regulated upstream by SIRT3-mediated PINK1 deacetylation, linking mitophagy signaling to PKM2 metabolic switching in chondrocytes.

    Evidence In vitro kinase assays, S127 mutagenesis, SIRT3/PINK1 conditional KO mice, metabolic flux and tetramer/dimer assays

    PMID:40087281

    Open questions at the time
    • Whether PINK1-PKM2 regulation operates in tissues beyond cartilage
    • Structural mechanism by which S127 phosphorylation stabilizes the tetramer interface

Open questions

Synthesis pass · forward-looking unresolved questions
  • The central unresolved question is whether PKM2 possesses intrinsic protein kinase activity: multiple labs report PEP-dependent phosphorylation of histone H3, STAT3, Bub3, and MLC2, yet rigorous reconstitution failed to detect direct activity, leaving the mechanism of PKM2's nuclear signaling functions—and whether they require enzymatic phosphotransfer or scaffolding/coactivator roles—fundamentally uncertain.
  • No consensus on protein kinase versus scaffolding mechanism
  • Structural basis of PEP-dependent phosphotransfer to protein substrates not resolved
  • In vivo quantitative contribution of PKM2 nuclear functions relative to its glycolytic role remains unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 8 GO:0140110 transcription regulator activity 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0003723 RNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 4 GO:0005840 ribosome 1
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 2
Partners
BUB3CTNNB1HIF1AJMJD5MFN2PGAM1PHGDHSTAT3

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 PKM2, but not PKM1, directly binds tyrosine-phosphorylated peptides via a phosphotyrosine-binding mechanism. Binding of phosphotyrosine peptides to PKM2 releases the allosteric activator fructose-1,6-bisphosphate (FBP), thereby inhibiting PKM2 enzymatic activity and diverting glucose metabolites from energy production to anabolic biosynthesis. Proteomic screen for phosphotyrosine-binding proteins, in vitro binding assays, enzymatic activity measurements, metabolic flux analysis Nature High 18337815
2009 Oncogenic FGFR1 directly phosphorylates PKM2 at Y105, which disrupts FBP cofactor binding and inhibits formation of active tetrameric PKM2, thereby suppressing pyruvate kinase activity, promoting aerobic glycolysis (Warburg effect), and supporting tumor growth. Y105 phosphorylation is common in human cancers. Phosphoproteomic analysis, in vitro kinase assays, Y105F point mutant rescue experiments, xenograft tumor growth assays Science Signaling High 19920251
2011 PKM2, but not PKM1, acts as a transcriptional coactivator for HIF-1α. PKM2 interacts directly with the HIF-1α subunit, enhances HIF-1 binding and p300 recruitment to hypoxia response elements, and promotes transactivation of glycolytic target genes. This interaction is potentiated by prolyl hydroxylase PHD3, which hydroxylates PKM2 at P403/P408, enhancing PKM2 binding to HIF-1α. Co-immunoprecipitation, in vitro binding assays, mass spectrometry for hydroxyproline detection, anti-hydroxyproline antibody assays, PHD3 knockdown, gene reporter assays Cell High 21620138
2011 EGFR activation induces nuclear translocation of PKM2 (but not PKM1), where PKM2 binds c-Src-phosphorylated Y333 of β-catenin at K433. This PKM2–β-catenin interaction is required for recruitment to the CCND1 promoter, removal of HDAC3, histone H3 acetylation, and cyclin D1 expression, thereby promoting tumor cell proliferation. Co-immunoprecipitation, nuclear fractionation, chromatin immunoprecipitation, site-directed mutagenesis, reporter assays, in vivo brain tumor model Nature High 22056988
2011 Reactive oxygen species (ROS) oxidize PKM2 at C358, inhibiting its enzymatic activity. This inhibition diverts glucose flux from glycolysis into the pentose phosphate pathway, increasing NADPH production and antioxidant capacity. A C358S oxidation-resistant PKM2 mutant sensitizes lung cancer cells to oxidative stress and impairs tumor xenograft formation. In vitro enzymatic assays, Cys358Ser mutagenesis, metabolic flux analysis, xenograft tumor model Science High 22052977
2011 Acetylation of PKM2 at K305 decreases its enzymatic activity and targets it for chaperone-mediated autophagy and subsequent lysosomal degradation. Biochemical acetylation assays, autophagy pathway analysis, lysosome inhibition experiments Cold Spring Harbor Symposia on Quantitative Biology Medium 22096030
2012 PKM2 acts as a protein kinase using phosphoenolpyruvate (PEP) as the phosphate donor to phosphorylate STAT3 at Y705 in the nucleus, activating MEK5 transcription and promoting cell proliferation. The dimeric form of PKM2 possesses protein kinase activity whereas the tetrameric form functions as a pyruvate kinase. In vitro phosphorylation assays with [32P]-PEP, nuclear localization studies, reporter assays, dimer-locked PKM2 mutant expression Molecular Cell Medium 22306293
2012 EGFR-activated ERK2 directly binds PKM2 (via Ile429/Leu431 docking groove interface) and phosphorylates PKM2 at S37. Phospho-S37 recruits PIN1 for cis-trans isomerization, which promotes PKM2 binding to importin α5 and nuclear translocation. Nuclear PKM2 then acts as a coactivator of β-catenin to induce c-Myc expression and upregulate glycolytic genes (GLUT1, LDHA, PKM2) in a positive feedback loop. Direct binding assays, in vitro kinase assay, PIN1 co-immunoprecipitation, S37A nuclear translocation-deficient mutant rescue, in vivo brain tumor model Nature Cell Biology High 23178880
2012 Nuclear PKM2 directly binds histone H3 and phosphorylates it at T11 upon EGF receptor activation. This phosphorylation causes dissociation of HDAC3 from CCND1 and MYC promoters and subsequent H3K9 acetylation, driving cyclin D1 and c-Myc expression, cell-cycle progression, and tumorigenesis. Direct binding assays (Co-IP, pulldown), in vitro kinase assay with recombinant histone H3, ChIP, mutagenesis, in vivo brain tumor model Cell High 22901803
2012 Serine is a natural allosteric activator of PKM2. Serine binds directly to PKM2 and activates its pyruvate kinase activity. In serine-deprived cells, PKM2 activity decreases, shifting cells to a fuel-efficient mode that diverts glucose carbon into serine biosynthesis. Direct binding assays, in vitro enzymatic activity measurements, metabolic flux analysis in serine-deprived cells Nature High 23064226
2009 Three hnRNP proteins — PTB (hnRNPI), hnRNPA1, and hnRNPA2 — bind repressively to sequences flanking exon 9 of PKM pre-mRNA, resulting in exon 10 (PKM2) inclusion and exclusion of exon 9 (PKM1). The oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1 ratio in cancer cells. RNA splicing assays, RNAi knockdown, RNA immunoprecipitation, promoter reporter assays, glioma tissue analysis Nature High 20010808
2010 In PKM2-expressing cells, PEP can directly phosphorylate the glycolytic enzyme PGAM1 at the catalytic histidine H11, providing an alternative glycolytic pathway that decouples ATP production from PEP-mediated phosphotransfer. This histidine-phosphorylated PGAM1 correlates with PKM2 expression in cancer cells and tumors. Mass spectrometry identification of phospho-His11-PGAM1, isotope-labeling metabolic flux assays, cancer cell line and tumor tissue correlations Science High 20847263
2011 mTOR activates the Warburg effect by inducing PKM2 expression via HIF-1α-mediated transcription and c-Myc/hnRNP-dependent regulation of PKM2 gene splicing. Disruption of PKM2 suppresses mTOR-mediated tumorigenesis. mTOR knockdown/inhibitor experiments, HIF-1α reporter assays, PKM splicing RT-PCR, mouse tumor models (TSC2-deficient), xenograft assays PNAS High 21325052
2013 JMJD5 directly interacts with PKM2 at the intersubunit interface region of PKM2, hindering PKM2 tetramerization and blocking pyruvate kinase activity. This JMJD5-PKM2 interaction also promotes nuclear translocation of PKM2 and enhances HIF-1α-mediated transactivation of glycolytic target genes. Co-immunoprecipitation, in vitro binding/tetramerization assays, pyruvate kinase activity assays, JMJD5 knockdown, ChIP, metabolic measurements PNAS High 24344305
2013 PKM2 (but not PKM1) binds the spindle checkpoint protein Bub3 during mitosis and phosphorylates Bub3 at Y207. This phosphorylation is required for Bub3-Bub1 complex recruitment to kinetochores and interaction with Blinkin, essential for correct kinetochore-microtubule attachment, mitotic checkpoint function, accurate chromosome segregation, and cell survival. Co-immunoprecipitation, in vitro kinase assay, Y207 phosphorylation-deficient mutant, kinetochore localization studies, chromosome segregation assays, in vivo brain tumor model Molecular Cell High 24316223
2014 Aurora B phosphorylates PKM2 (but not PKM1) at T45 during mitosis, which is required for PKM2 localization to the contractile ring and interaction with myosin light chain 2 (MLC2). PKM2 then phosphorylates MLC2 at Y118, priming ROCK2 binding and subsequent ROCK2-dependent S15 phosphorylation of MLC2, regulating cytokinesis. Co-immunoprecipitation, in vitro kinase assays, T45 and Y118 phosphorylation mutants, subcellular localization studies, cytokinesis assays, in vivo brain tumor model Nature Communications High 25412762
2014 PKM2 interacts with Oct4 in glioma stem cells, and this interaction is implicated in control of glioma spheroid differentiation. Modulation of PKM2/Oct4 complexes (e.g., by DCA) inhibits Oct4-dependent gene expression. Co-immunoprecipitation, glioma spheroid differentiation assays, PKM2 silencing, DCA treatment Cell Death & Disease Medium 24481450
2015 Using [32P]-PEP labeling with recombinant enzyme and PKM2 genetic deletion in vitro, no PKM2-dependent direct protein phosphorylation could be detected; most observed phospholabeling depended on ADP, not PKM2. This study challenges the proposed role of PKM2 as a direct protein kinase. [32P]-PEP phosphorylation assay, recombinant PKM2, PKM2-null cell extracts, in vitro reconstitution Molecular Cell High 26300261
2015 PTBP1 upregulation in gemcitabine-resistant pancreatic cancer cells promotes PKM2 isoform expression by increased recruitment to PKM pre-mRNA. Knockdown of PTBP1 reduces PKM2 and restores gemcitabine sensitivity. Switching PKM splicing from PKM2 to PKM1 via antisense oligonucleotides also rescues drug sensitivity. RT-PCR splicing assays, PTBP1 RIP, antisense oligonucleotide PKM splice-switching, drug resistance assays, PTBP1 knockdown Oncogene High 26234680
2016 EGFR activation triggers c-Src-mediated phosphorylation of Cdc25A at Y59, enabling Cdc25A interaction with nuclear PKM2. Cdc25A dephosphorylates PKM2 at S37, promoting PKM2-dependent β-catenin transactivation, upregulation of glycolytic genes (GLUT1, PKM2, LDHA), and CDC25A itself in a positive feedback loop driving the Warburg effect and tumorigenesis. Co-immunoprecipitation, in vitro phosphatase assay (Cdc25A on PKM2), mutagenesis, reporter assays, in vivo brain tumor model Nature Communications High 27485204
2016 PKM2-mediated glycolysis promotes inflammasome (NLRP3 and AIM2) activation in macrophages by modulating EIF2AK2 (PKR) phosphorylation. Pharmacological or genetic inhibition of PKM2 or EIF2AK2 attenuates inflammasome activation and IL-1β/IL-18/HMGB1 release. Myeloid cell-specific PKM2 knockout protects mice from septic death. Myeloid-specific PKM2 conditional knockout, PKM2 inhibitor pharmacology, EIF2AK2 knockdown, inflammasome activation assays, in vivo endotoxemia/sepsis models Nature Communications High 27779186
2019 PKM2 interacts with mitofusin 2 (MFN2) to promote mitochondrial fusion and oxidative phosphorylation while attenuating glycolysis. mTOR phosphorylates MFN2, increasing the PKM2:MFN2 interaction and modulating metabolic balance. Thus an mTOR-MFN2-PKM2 axis coordinates glycolysis and OXPHOS. Co-immunoprecipitation, mitochondrial morphology imaging, metabolic flux measurements, mTOR inhibition, MFN2 knockdown Protein & Cell Medium 30887444
2020 PKM2 translocates to the nucleus in Th17 cells and interacts with STAT3, enhancing STAT3 activation (phosphorylation) and thereby increasing Th17 cell differentiation. T cell-specific PKM2 deletion impairs Th17 differentiation and ameliorates experimental autoimmune encephalomyelitis (EAE) without affecting metabolic reprogramming or proliferative capacity. T cell-specific conditional PKM2 knockout, nuclear fractionation, Co-immunoprecipitation of PKM2-STAT3, EAE in vivo model, flow cytometry for Th17 differentiation Journal of Experimental Medicine High 32697823
2020 Pkm2 regulates the cardiomyocyte cell cycle and reduces oxidative stress through anabolic pathways and β-catenin signaling. Cardiomyocyte-specific Pkm2 deletion reduces cardiomyocyte number and myocardial size, while Pkm2 mRNA delivery after myocardial infarction increases cardiomyocyte division, cardiac function, and survival. Cardiomyocyte-specific knockout mice, modified mRNA delivery, myocardial infarction model, cell cycle markers, β-catenin pathway analysis Circulation High 32078387
2020 Annexin A5 directly interacts with PKM2 at residues D101, L104, and R106, inhibits Y105 phosphorylation, and promotes PKM2 tetramer formation, thereby switching macrophage metabolism from glycolysis to OXPHOS and shifting macrophage polarization from M1 to M2. Pull-down, Co-IP, molecular docking, Y105E phosphomimetic mutant, compound 3k inhibitor, in vivo NASH mouse model Redox Biology Medium 32863213
2021 PKM2 acts as a histidine kinase using PEP as phosphate donor to phosphorylate PGAM1 at H11. Monomeric and dimeric (but not tetrameric) PKM2 are the efficient forms for this reaction. EGF signaling triggers Src-catalyzed PGAM1 Y119 phosphorylation, which is a prerequisite for PKM2 binding and subsequent PGAM1 H11 phosphorylation, constituting a cancer-specific regulatory mechanism. In vitro kinase assays with PEP as donor, mass spectrometry for H11 phosphorylation, PKM2 oligomeric form separation, PGAM1 Y119F and H11A mutants, cell-permeable pY119 peptide disruption, tumor growth assays EMBO Journal High 38750259
2021 PKM2 regulates lipid homeostasis via an ER transmembrane protein TMEM33. Loss of PKM2 upregulates TMEM33, which recruits the E3 ligase RNF5 to degrade SCAP, reducing SREBP activation and lipid synthesis. TMEM33 is transcriptionally regulated by NRF1, whose activation is controlled by PKM2 levels. PKM2 knockout cells and mice, TMEM33 identification by proteomics, Co-IP for RNF5-SCAP interaction, SREBP reporter assays, TEPP-46 PKM2 activation EMBO Journal Medium 34487377
2022 Lactylation of PKM2 at K62 (by lactate) inhibits its tetramer-to-dimer transition, thereby promoting pyruvate kinase activity and reducing nuclear PKM2 distribution, which suppresses the Warburg effect and promotes transition from pro-inflammatory to reparative macrophage phenotype. Lactylation proteomics, Co-IP, K62 site mutagenesis, tetramer/dimer ratio assays, enzymatic activity measurement, nuclear fractionation, macrophage polarization assays International Journal of Biological Sciences Medium 36439872
2022 FSTL1 binds directly to PKM2 via its FK domain, promotes PKM2 phosphorylation and nuclear translocation, and reduces PKM2 ubiquitination, thereby enhancing PKM2-dependent glycolysis and M1 macrophage polarization promoting liver fibrosis. Co-immunoprecipitation, myeloid-specific FSTL1 KO mice, PKM2 activator (DASA-58) rescue, in vitro glycolysis assays, three murine fibrosis models Gut Medium 35140065
2022 PKM2 in myeloid/neutrophil cells promotes STAT3 phosphorylation to regulate post-ischemic neuroinflammation. Myeloid-specific PKM2 deletion reduces neutrophil hyperactivation, NET formation, and cerebral thromboinflammation after stroke, improving functional outcomes. Inhibiting PKM2 nuclear translocation with a small molecule recapitulates these effects. Myeloid cell-specific PKM2 knockout mice, stroke models, laser speckle imaging, nuclear PKM2 inhibitor, flow cytometry, STAT3 phosphorylation assays Blood High 34529778
2022 Celastrol covalently binds to C424 of PKM2 (identified by ABPP, CETSA, and SPR), inhibiting its enzymatic activity and suppressing aerobic glycolysis (Warburg effect) and inflammation in sepsis models. Activity-based protein profiling (ABPP), CETSA, SPR, Cys424 point mutagenesis, enzymatic activity assays, in vivo endotoxemia/sepsis models Military Medical Research Medium 35596191
2022 PKM2 palmitoylation at C31 (mediated by the palmitoyl acyltransferase zDHHC13) impairs PKM2 tetramerization, inhibits its pyruvate kinase activity, and reduces endothelial glycolysis. C31S mutation or endothelial AAV delivery of C31S PKM2 prevents palmitic acid-induced cardiovascular dysfunction in ApoE−/− mice. Palmitoyl-proteomics, C31S point mutant, palmitoylation inhibitor 2-BP, depalmitoylase inhibitor ML349, endothelial AAV gene delivery, cardiovascular function assays, zDHHC13 identification Advanced Science High 39665133
2023 PHGDH physically interacts with PKM2, preventing PCAF-catalyzed K305 acetylation and subsequent autophagic degradation of PKM2. PHGDH also facilitates p300-catalyzed PKM2 K433 acetylation, which promotes PKM2 nuclear translocation and stimulates PKM2-dependent H3T11 phosphorylation to regulate transcription of senescence-associated genes, thereby preventing endothelial cell senescence. Co-immunoprecipitation, K305 and K433 acetylation mapping, PCAF/p300 knockdown, autophagy inhibitor experiments, H3T11 phosphorylation assays, in vivo aging mouse model Nature Communications High 36899022
2023 JMJD4 hydroxylates PKM2 at K66, which facilitates Hsp70-mediated chaperone-mediated autophagy degradation of Pkm2. Loss of Jmjd4 in cardiomyocytes causes Pkm2 accumulation, impaired mitochondrial respiration, and spontaneous dilated cardiomyopathy. Enhancing PKM2 tetramer activity with TEPP-46 rescues Jmjd4-deficient DCM. Cardiomyocyte-specific Jmjd4 knockout mice, mass spectrometry for K66 hydroxylation, Hsp70 Co-IP, CMA assays, TEPP-46 pharmacologic rescue, cardiac function assays Circulation High 37066795
2023 PKM interacts with ribosomes in a poly-ADP ribosylation (PARylation)-dependent manner and causes translational stalling near lysine- and glutamate-encoding sequences in cytosolic (ER-excluded) mRNAs. PKM-ribosome interaction is regulated by ADP levels, linking carbohydrate metabolism to mRNA translation. Polysome fractionation proteomics, eCLIP-seq for PKM-mRNA crosslinks, ribosome footprint protection sequencing, ADP titration experiments, PARylation inhibition Nucleic Acids Research Medium 37224531
2024 Nuclear PKM2 functions as a non-canonical RNA-binding protein that specifically binds folded RNA G-quadruplex (rG4) structures in pre-mRNAs. PKM2 occupancy at rG4s prevents binding of repressive RBPs (e.g., HNRNPF) and promotes expression of rG4-containing pre-mRNAs (the 'rG4ome'), supporting epithelial-to-mesenchymal transition and cancer cell invasion. eCLIP-seq for nuclear PKM2-RNA interactions, rG4 structure probing, HNRNPF competition assays, PKM2 nuclear accumulation prevention, xenograft invasion model Molecular Cell High 39153475
2024 SIRT1 interacts with PKM2 and deacetylates it at K135 and K206, reducing PKM2 enzyme activity and lactate production. This suppresses glial activation in the brain and alleviates Parkinson's disease-like phenotypes in mice. Co-immunoprecipitation, in vitro deacetylation assays, K135/K206 site-specific analysis, SIRT1 knockdown/overexpression, PKM2 overexpression/inhibition in PD mouse models Cell Reports Medicine Medium 39128469
2024 PKM2 aggregates form in senescent cells and organs of aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cellular senescence. Small molecules that dissolve PKM2 aggregates alleviate senescence signatures and extend lifespan in aged mice. Aggregate detection in senescent cells and aged tissue, enzymatic activity assays, small molecule screen (K35, K27), senescence marker assays, mouse lifespan studies Nature Communications Medium 38982055
2025 PINK1 phosphorylates PKM2 at S127, preserving its active tetrameric form, which inhibits nuclear translocation and interaction with β-catenin, resulting in a metabolic shift toward OXPHOS. SIRT3 deacetylates PINK1 to promote this mitophagy-linked PKM2 regulation, collectively protecting against osteoarthritis-associated cartilage degeneration. SIRT3/PINK1 conditional KO mice, in vitro kinase assays, S127 mutagenesis, Co-IP of PKM2-β-catenin, metabolic flux assays, PKM2 tetramer/dimer assays Bone Research Medium 40087281
2025 March2 (E3 ubiquitin ligase) promotes K33-linked polyubiquitination of PKM2, facilitating PKM2 dimer-to-tetramer conversion. Loss of March2 in vascular smooth muscle cells reduces PKM2 tetramerization, promotes nuclear PKM2 and H3K18 lactylation, and exacerbates aortic aneurysm/dissection via p53-driven apoptosis. TEPP-46 (PKM2 tetramer activator) rescues this pathology. March2 smooth muscle cell-specific KO mice, Co-IP, ubiquitination assays with K33-linkage specificity, PKM2 tetramer/dimer assays, H3K18 lactylation analysis, TEPP-46 rescue, aortic dissection model Circulation Research Medium 40079144

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2011 Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 1209 21620138
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2011 Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science (New York, N.Y.) 969 22052977
2009 HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 948 20010808
2004 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature biotechnology 916 15592455
2011 Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 914 22056988
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2008 Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 819 18337815
2012 ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nature cell biology 769 23178880
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2003 Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. The Journal of biological chemistry 708 12519789
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 696 22901803
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2009 Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Science signaling 652 19920251
2012 Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Molecular cell 648 22306293
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2001 Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 564 11487543
2012 Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 535 23064226
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2010 Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science (New York, N.Y.) 524 20847263
2011 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 507 21565611
2011 Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proceedings of the National Academy of Sciences of the United States of America 494 21325052
2016 PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nature communications 451 27779186
2016 PKM2, cancer metabolism, and the road ahead. EMBO reports 432 27856534
2019 PKM2, function and expression and regulation. Cell & bioscience 389 31391918
2020 Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis. Frontiers in oncology 388 32195169
2012 Emerging roles of PKM2 in cell metabolism and cancer progression. Trends in endocrinology and metabolism: TEM 307 22824010
2022 Lactylation of PKM2 Suppresses Inflammatory Metabolic Adaptation in Pro-inflammatory Macrophages. International journal of biological sciences 293 36439872
2013 JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. Proceedings of the National Academy of Sciences of the United States of America 261 24344305
2013 PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory. Nature 246 23283174
2016 PKM2 and cancer: The function of PKM2 beyond glycolysis. Oncology letters 244 26998110
2020 Pkm2 Regulates Cardiomyocyte Cell Cycle and Promotes Cardiac Regeneration. Circulation 236 32078387
2020 PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. The Journal of experimental medicine 227 32697823
2020 Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics. Cancer letters 199 33246091
2013 PKM2 regulates chromosome segregation and mitosis progression of tumor cells. Molecular cell 196 24316223
2015 Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells. Oncogene 193 26234680
2019 PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation. Protein & cell 192 30887444
2022 FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of PKM2. Gut 191 35140065
2016 PKM2 dephosphorylation by Cdc25A promotes the Warburg effect and tumorigenesis. Nature communications 155 27485204
2020 Annexin A5 regulates hepatic macrophage polarization via directly targeting PKM2 and ameliorates NASH. Redox biology 149 32863213
2022 PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke. Blood 126 34529778
2014 The multifaceted regulation and functions of PKM2 in tumor progression. Biochimica et biophysica acta 122 25064846
2014 PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells. Nature communications 122 25412762
2022 Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect. Military Medical Research 106 35596191
2022 ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth. Cancer research 103 34921016
2011 Regulation of glycolysis and gluconeogenesis by acetylation of PKM and PEPCK. Cold Spring Harbor symposia on quantitative biology 100 22096030
2019 Targeting the miR-122/PKM2 autophagy axis relieves arsenic stress. Journal of hazardous materials 95 31546213
2022 Myeloid Cell PKM2 Deletion Enhances Efferocytosis and Reduces Atherosclerosis. Circulation research 94 35400205
2015 Lack of Evidence for PKM2 Protein Kinase Activity. Molecular cell 92 26300261
2023 Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence. Nature communications 91 36899022
2022 PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing. Circulation research 81 36200440
2023 HNRNPL induced circFAM13B increased bladder cancer immunotherapy sensitivity via inhibiting glycolysis through IGF2BP1/PKM2 pathway. Journal of experimental & clinical cancer research : CR 79 36747239
2014 Control of glioma cell death and differentiation by PKM2-Oct4 interaction. Cell death & disease 74 24481450
2018 Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect. Frontiers in cell and developmental biology 68 30087897
2019 Benserazide is a novel inhibitor targeting PKM2 for melanoma treatment. International journal of cancer 67 31652354
2022 GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism. Redox biology 65 36116159
2020 E3 ligase ZFP91 inhibits Hepatocellular Carcinoma Metabolism Reprogramming by regulating PKM splicing. Theranostics 63 32754263
2021 Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm. Frontiers in immunology 54 34759927
2022 PKM2 Is Essential for Bladder Cancer Growth and Maintenance. Cancer research 52 34903602
2021 FOXM1D potentiates PKM2-mediated tumor glycolysis and angiogenesis. Molecular oncology 52 33314660
2021 Mechanism of PKM2 affecting cancer immunity and metabolism in Tumor Microenvironment. Journal of Cancer 52 33995634
2019 PKM2: A Potential Regulator of Rheumatoid Arthritis via Glycolytic and Non-Glycolytic Pathways. Frontiers in immunology 52 31921178
2021 PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability. The EMBO journal 50 34487377
2019 PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production. Scientific reports 48 31636306
2022 The Role of PKM2 in the Regulation of Mitochondrial Function: Focus on Mitochondrial Metabolism, Oxidative Stress, Dynamic, and Apoptosis. PKM2 in Mitochondrial Function. Oxidative medicine and cellular longevity 46 35571239
2019 Glycolytic Enzyme PKM2 Mediates Autophagic Activation to Promote Cell Survival in NPM1-Mutated Leukemia. International journal of biological sciences 46 30906218
2024 LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM. Molecular cancer 45 38263157
2017 PKM2 in carcinogenesis and oncotherapy. Oncotarget 45 29299177
2017 Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells. Oncotarget 43 28498807
2024 SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2. Cell reports. Medicine 42 39128469
2023 Jmjd4 Facilitates Pkm2 Degradation in Cardiomyocytes and Is Protective Against Dilated Cardiomyopathy. Circulation 40 37066795
2018 PKM2 and HIF-1α regulation in prostate cancer cell lines. PloS one 40 30216369
2024 Palmitic Acid Accelerates Endothelial Cell Injury and Cardiovascular Dysfunction via Palmitoylation of PKM2. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 39 39665133
2014 Activators of PKM2 in cancer metabolism. Future medicinal chemistry 39 25078136
2013 Does PKM(zeta) maintain memory? Brain research bulletin 38 24076105
2022 Dihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS. Acta pharmaceutica Sinica. B 37 36815040
2020 Modulation of PKM activity affects the differentiation of TH17 cells. Science signaling 35 33109748
2022 Inhibition of PKM2 Enhances Sensitivity of Olaparib to Ovarian Cancer Cells and Induces DNA Damage. International journal of biological sciences 34 35280680
2022 Bile acids attenuate PKM2 pathway activation in proinflammatory microglia. Scientific reports 33 35087114
2021 Targeting pyruvate kinase muscle isoform 2 (PKM2) in cancer: What do we know so far? Life sciences 33 34102192
2022 Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation. Cell reports 32 36450257
2024 METTL1 mediates PKM m7G modification to regulate CD155 expression and promote immune evasion in colorectal cancer. Journal of translational medicine 30 39741310
2018 Lapatinib Inhibits Breast Cancer Cell Proliferation by Influencing PKM2 Expression. Technology in cancer research & treatment 30 29343208
2025 Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine. Cell reports 28 39772395
2022 Research progress on the role of PKM2 in the immune response. Frontiers in immunology 27 35967360
2024 The role of PKM2 in cancer progression and its structural and biological basis. Journal of physiology and biochemistry 26 38329688
2024 PKM2 functions as a histidine kinase to phosphorylate PGAM1 and increase glycolysis shunts in cancer. The EMBO journal 26 38750259
2021 SAM68 promotes tumorigenesis in lung adenocarcinoma by regulating metabolic conversion via PKM alternative splicing. Theranostics 26 33537092
2021 Tumor suppressor SMAR1 regulates PKM alternative splicing by HDAC6-mediated deacetylation of PTBP1. Cancer & metabolism 26 33863392
2016 G9a inhibition induced PKM2 regulates autophagic responses. The international journal of biochemistry & cell biology 26 27417236
2021 Emodin ameliorates antioxidant capacity and exerts neuroprotective effect via PKM2-mediated Nrf2 transactivation. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 25 34971761
2018 miR-625-5p/PKM2 negatively regulates melanoma glycolysis state. Journal of cellular biochemistry 25 30500994
2025 SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch. Bone research 24 40087281
2021 Parthenolide Derivatives as PKM2 Activators Showing Potential in Colorectal Cancer. Journal of medicinal chemistry 24 34847663
2022 Role of Pyruvate Kinase M2 (PKM2) in Cardiovascular Diseases. Journal of cardiovascular translational research 22 36178660
2021 Dexamethasone Promotes Aspergillus fumigatus Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2. Journal of fungi (Basel, Switzerland) 22 33498318
2023 The interaction between apigenin and PKM2 restrains progression of colorectal cancer. The Journal of nutritional biochemistry 21 37597817
2024 LncRNA PWRN1 inhibits the progression of hepatocellular carcinoma by activating PKM2 activity. Cancer letters 20 38218456
2021 A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme. Metabolic brain disease 20 33651273
2022 JOSD2 regulates PKM2 nuclear translocation and reduces acute myeloid leukemia progression. Experimental hematology & oncology 19 35836282
2022 CircRNA SRRM4 affects glucose metabolism by regulating PKM alternative splicing via SRSF3 deubiquitination in epilepsy. Neuropathology and applied neurobiology 19 36168302
2024 PKM2 aggregation drives metabolism reprograming during aging process. Nature communications 18 38982055
2024 PTBP1 crotonylation promotes colorectal cancer progression through alternative splicing-mediated upregulation of the PKM2 gene. Journal of translational medicine 18 39497094
2023 Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling. Nucleic acids research 18 37224531
2022 PKM2 Modulation in Head and Neck Squamous Cell Carcinoma. International journal of molecular sciences 18 35054968
2024 LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39342418
2023 Simultaneous suppression of PKM2 and PHGDH elicits synergistic anti-cancer effect in NSCLC. Frontiers in pharmacology 17 37284309
2023 Glycolytic enzyme PKM2 regulates cell senescence but not inflammation in the process of osteoarthritis. Acta biochimica et biophysica Sinica 17 37525533
2023 The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases. Molecular neurobiology 16 38157121
2021 Dual Covalent Inhibition of PKM and IMPDH Targets Metabolism in Cutaneous Metastatic Melanoma. Cancer research 16 34099492
2024 N6-methyladenosine-modified SRPK1 promotes aerobic glycolysis of lung adenocarcinoma via PKM splicing. Cellular & molecular biology letters 15 39095708
2022 The CXCL12/CXCR4/ACKR3 Signaling Axis Regulates PKM2 and Glycolysis. Cells 15 35681470
2020 Regulation of trophoblast cell invasion by Pyruvate Kinase isozyme M2 (PKM2). Placenta 15 33070034
2024 Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications. Current medicinal chemistry 14 37455458
2024 PKM2 induces mitophagy through the AMPK-mTOR pathway promoting CSFV proliferation. Journal of virology 14 38319105
2024 Nuclear PKM2 binds pre-mRNA at folded G-quadruplexes and reveals their gene regulatory role. Molecular cell 14 39153475
2021 Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers. Cancers 14 33478099
2025 March2 Alleviates Aortic Aneurysm/Dissection by Regulating PKM2 Polymerization. Circulation research 13 40079144
2023 RBX1 regulates PKM alternative splicing to facilitate anaplastic thyroid carcinoma metastasis and aerobic glycolysis by destroying the SMAR1/HDAC6 complex. Cell & bioscience 13 36810109
2023 Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review. Medicine 13 37861491