Affinage

PGK1

Phosphoglycerate kinase 1 · UniProt P00558

Length
417 aa
Mass
44.6 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PGK1 is a glycolytic phosphoglycerate kinase that catalyzes the reversible conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate (Km for 1,3-BPG ~6.86 µM, for 3-PG ~186 µM), yet siRNA depletion across five cancer lines alters upstream glycolytic intermediates without substantially changing flux, indicating its enzymatic role is not flux-limiting in those settings (PMID:32217690). Beyond catalysis, PGK1 moonlights as a protein kinase whose substrate selection is dictated by localization and post-translational modification. Oncogenic ERK signaling phosphorylates PGK1 at S203, triggering PIN1-mediated isomerization and mitochondrial import where PGK1 phosphorylates PDHK1 at T338 to suppress the PDH complex and shift metabolism toward glycolysis (PMID:26942675); T255 O-GlcNAcylation drives the same mitochondrial translocation and PDH inhibition while activating glycolytic output (PMID:31911580). PGK1 protein kinase activity depends on intermolecular autophosphorylation at Y324, which PTEN reverses by dephosphorylation (PMID:31492635). In the nucleus, CK2α-mediated S256 phosphorylation enables PGK1 to bind CDC7 and regenerate ATP from CDC7-derived ADP, relieving allosteric inhibition of DNA replication (PMID:30392930). Under metabolic stress, NAA10-dependent K388 acetylation redirects PGK1 to phosphorylate Beclin1-S30 and initiate autophagy, with substrate binding switching between PRAS40 (normoxia) and Beclin1 (hypoxia) (PMID:28486006, PMID:35058442). A dense layer of modifications tunes its activities: K323 acetylation (PCAF writer, SIRT7 eraser) activates the enzyme (PMID:27774669), K220 acetylation (KAT9 writer, HDAC3 eraser) inhibits it by blocking ADP binding (PMID:26356530), T243 phosphorylation by PDPK1 alters substrate affinity to favor glycolysis (PMID:30029001), R206 methylation by PRMT1 promotes S203 phosphorylation (PMID:38402202), and succinylation, crotonylation, and ubiquitination further regulate stability and activity (PMID:38441561, PMID:39134530, PMID:36807568). PGK1 also functions extracellularly, binding neuronal Enolase-2 to promote motoneuron neurite outgrowth via Rac1/Pak1/P38/Limk1/Cofilin signaling (PMID:31361595, PMID:37582937), and pharmacological inhibition of PGK1 activates the Keap1/NRF2 antioxidant cascade through methylglyoxal modification of Keap1 (PMID:32649311, PMID:36386479).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2009 Low

    Early genetic work asked whether PGK1 had functions beyond glycolytic catalysis, establishing non-canonical cytoprotective and signaling roles.

    Evidence Multicopy suppressor screen in yeast lsm4 mutants and PGK1 overexpression in prostate cancer bone metastasis models

    PMID:19180641 PMID:19825988

    Open questions at the time
    • No biochemical mechanism for the anti-apoptotic or osteoblast-inducing effects
    • Yeast suppression not linked to a defined human pathway
  2. 2015 High

    Acetylation at K220 was shown to inhibit PGK1 by disrupting ADP binding, with KAT9 as writer and HDAC3 (insulin/PI3K/AKT/mTOR-regulated) as eraser, establishing reversible acetylation as a metabolic control switch.

    Evidence MS site mapping, enzymatic assays, mutagenesis, and HDAC3 phosphorylation/pathway manipulation

    PMID:26356530

    Open questions at the time
    • Structural basis of ADP-binding disruption not resolved
    • Single lab
  3. 2016 High

    PGK1 was identified as a bona fide protein kinase: ERK-driven S203 phosphorylation and PIN1 isomerization route it to mitochondria to phosphorylate PDHK1-T338, coupling oncogenic signaling to a glycolytic shift, while K323 acetylation independently tunes its enzymatic activity.

    Evidence In vitro kinase assays, mitochondrial import assays, mutagenesis, xenografts; separate MS/enzymatic work on PCAF/SIRT7-regulated K323

    PMID:26942675 PMID:27774669

    Open questions at the time
    • Structural basis of PGK1 kinase activity not defined
    • How mitochondrial PGK1 is retained/imported mechanistically incomplete
  4. 2017 High

    Stress-induced K388 acetylation by NAA10 was shown to switch PGK1 to an autophagy-initiating kinase that phosphorylates Beclin1-S30, linking nutrient sensing to autophagy.

    Evidence In vitro kinase assays, mutagenesis at K388/S30, autophagy flux assays, xenografts

    PMID:28486006

    Open questions at the time
    • How acetylation reprograms substrate selection structurally unknown
  5. 2018 High

    Distinct phosphorylation events were mapped to specific outputs: PDPK1-driven T243 phosphorylation enhances glycolysis, and CK2α-driven S256 phosphorylation enables nuclear PGK1 to regenerate ATP for CDC7 and promote DNA replication.

    Evidence In vitro kinase/ATPase and ADP-ATP conversion assays, Co-IP, nuclear fractionation, mutagenesis, xenografts

    PMID:30029001 PMID:30392930

    Open questions at the time
    • Stoichiometry of nuclear ATP regeneration in vivo unquantified
    • Coordination among competing modifications unresolved
  6. 2019 High

    The activation/inactivation logic of PGK1 kinase function was defined: intermolecular Y324 autophosphorylation activates it and PTEN dephosphorylates Y324 to switch it off; subcellular distribution dictates proliferative vs. metastatic outcomes; extracellular PGK1 was tied to motoneuron outgrowth.

    Evidence In vitro phosphatase/kinase reconstitution, Y324F knockin mice, ChIP/reporter assays for SMAD4, recombinant Pgk1 rescue in zebrafish/SOD1 models

    PMID:31361595 PMID:31492635 PMID:31611300

    Open questions at the time
    • Nuclear-vs-cytoplasmic functional split mechanistically incomplete (Medium)
    • Receptor for extracellular PGK1 not yet identified at this stage
  7. 2020 High

    Rigorous kinetic and knockdown analysis showed PGK1's glycolytic activity is not flux-limiting in tested cancer lines, while O-GlcNAcylation at T255 was identified as a driver of both glycolytic activation and mitochondrial PDH inhibition; PGK1 was also placed upstream of the Keap1/NRF2 antioxidant axis.

    Evidence Forward-reaction kinetic assay with defined Km, multi-cell-line siRNA plus metabolite profiling; MS site mapping of T255; CBR-470-1 inhibition and CRISPR KO with Nrf2 reporters

    PMID:31911580 PMID:32217690 PMID:32649311

    Open questions at the time
    • Reconciliation between non-limiting flux and pro-tumor phenotypes incomplete
    • Keap1 link lacks direct biochemical reconstitution (Medium)
  8. 2022 Medium

    Oxygen-dependent substrate switching (PRAS40 under normoxia, Beclin1 under hypoxia) and stability control via KIF15/USP10 deubiquitination expanded the regulatory and kinase-target repertoire of PGK1.

    Evidence Co-IP, in vitro kinase and ubiquitination assays, KIF15 truncation mapping, autophagy and glycolysis assays, xenografts

    PMID:35058442 PMID:36807568

    Open questions at the time
    • Single-lab findings without reciprocal validation
    • Molecular trigger of substrate switching not defined
  9. 2023 Medium

    PGK1's extracellular receptor (neural Enolase-2) was mapped, and additional interactions (NLRP3, GSK3β/Hsp90, neurodegeneration condensate clearance) broadened its signaling reach.

    Evidence Domain-truncation binding/immunoEM for ENE2, Co-IP for NLRP3 and GSK3β-Hsp90, ATP/aggregate imaging in neurodegeneration models

    PMID:34403222 PMID:37249790 PMID:37582937 PMID:39080660

    Open questions at the time
    • Direct phosphorylation of NLRP3 not site-mapped
    • Several interactions rest on single Co-IP evidence
  10. 2024 Medium

    A further set of modifications—R206 methylation, K191/K192 succinylation, and K131/K156/K220 crotonylation—were shown to tune PGK1 stability and the glycolysis-vs-mitochondrial balance, embedding PGK1 in HIF1α/ATF3 and ECHS1-controlled circuits.

    Evidence MS/proteomic site mapping, ChIP for P4HA1 regulation, Co-IP of ECHS1, metabolic/Seahorse assays, mutagenesis, in vivo models

    PMID:38402202 PMID:38441561 PMID:39134530

    Open questions at the time
    • Combinatorial interplay among the many PTMs not modeled
    • Single-lab observations

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dense set of competing modifications and localization cues are integrated in vivo to select between PGK1's glycolytic, mitochondrial-kinase, nuclear-kinase, autophagic, and extracellular functions remains unresolved.
  • No structural model explaining how PGK1 acquires protein-kinase activity
  • Hierarchy/crosstalk among S203, T243, S256, Y324, T255 and acetylation/methylation sites unknown
  • Physiological versus oncogenic contributions of moonlighting functions not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005576 extracellular region 3 GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 2 R-HSA-69306 DNA Replication 1
Partners
BECN1CDC7ENO2HSP90NLRP3PDHK1PRAS40PTEN

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Hypoxia, EGFR activation, and oncogenic Ras/Raf mutations induce ERK-dependent PGK1 S203 phosphorylation, which triggers PIN1-mediated cis-trans isomerization and subsequent mitochondrial translocation of PGK1. Inside mitochondria, PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1) at T338, activating PDHK1 to phosphorylate and inhibit the pyruvate dehydrogenase (PDH) complex, thereby suppressing mitochondrial pyruvate utilization and promoting glycolysis. In vitro kinase assay, Co-IP, site-directed mutagenesis, subcellular fractionation, mitochondrial import assay, xenograft tumor model Molecular cell High 26942675
2020 PGK1 is O-GlcNAcylated at threonine 255 (T255), which activates its glycolytic enzymatic activity to enhance lactate production and simultaneously induces PGK1 translocation into mitochondria, where PGK1 phosphorylates and inhibits the pyruvate dehydrogenase (PDH) complex. Blocking T255 O-GlcNAcylation decreases glycolysis and suppresses tumor growth. Mass spectrometry, site-directed mutagenesis, subcellular fractionation, in vitro kinase assay, glycolysis assays, xenograft model Nature communications High 31911580
2018 M2 macrophage-secreted IL-6 activates PDPK1, which phosphorylates PGK1 at threonine 243 (T243). This phosphorylation alters PGK1 substrate affinity to facilitate the glycolytic reaction, promoting aerobic glycolysis, tumor cell proliferation, and tumorigenesis. In vitro kinase assay, Co-IP, site-directed mutagenesis, glycolysis assays, xenograft model, human GBM tissue analysis Molecular cell High 30029001
2016 PGK1 is acetylated at lysine 323 (K323) by the acetyltransferase PCAF, which activates its enzymatic activity. SIRT7 deacetylates K323 to reverse this activation. K323 acetylation promotes cancer cell metabolism and liver cancer cell proliferation. Mass spectrometry, site-directed mutagenesis, enzymatic activity assays, Co-IP, knockdown/overexpression in cancer cell lines Hepatology (Baltimore, Md.) High 27774669
2015 PGK1 is acetylated at lysine 220 (K220) by KAT9, which inhibits PGK1 activity by disrupting ADP binding. HDAC3 deacetylates K220, an event promoted by the insulin/PI3K/AKT/mTOR pathway through HDAC3 S424 phosphorylation, which enhances HDAC3-PGK1 interaction. Deacetylation at K220 stimulates PGK1 glycolytic activity. Mass spectrometry, site-directed mutagenesis, enzymatic activity assays, Co-IP, HDAC3 phosphorylation mutants, insulin signaling pathway manipulation PLoS biology High 26356530
2019 PTEN directly interacts with PGK1 and uses its protein phosphatase activity to dephosphorylate PGK1 at autophosphorylated Y324, inhibiting PGK1 kinase activity. PGK1 autophosphorylates itself at Y324 in an intermolecular fashion to activate its protein kinase function. PGK1 Y324F knockin mice show inhibited brain tumor formation. Co-IP, in vitro phosphatase assay, in vitro kinase assay, site-directed mutagenesis, knockin mouse model, glycolysis assays, human GBM tissue analysis Molecular cell High 31492635
2017 Under glutamine deprivation or hypoxia, PGK1 is acetylated at K388 by NAA10/ARD1 in an mTOR-inhibition-dependent manner, leading to interaction between PGK1 and BECN1 (Beclin 1) and subsequent phosphorylation of BECN1 at S30 by PGK1. This phosphorylation enhances ATG14-associated PIK3C3/VPS34 complex activity, increasing PtdIns3P generation to initiate autophagy. Co-IP, in vitro kinase assay, site-directed mutagenesis, autophagy flux assays, knockdown/overexpression, xenograft model Autophagy High 28486006
2018 Nuclear PGK1 is phosphorylated at S256 by CK2α (activated by EGFR/ERK signaling), enabling PGK1 interaction with CDC7. CDC7-bound PGK1 converts ADP (product of CDC7 kinase activity) back to ATP, thereby relieving ADP-mediated allosteric inhibition of the CDC7-ASK complex and promoting DNA replication and cell proliferation. Co-IP, in vitro kinase/ATPase assays, ADP-ATP conversion assay, nuclear fractionation, site-directed mutagenesis, DNA replication assays, xenograft model Molecular cell High 30392930
2014 Terazosin binds directly to PGK1 and activates its enzymatic activity, likely by promoting ATP release. The ATP generated by PGK1 enhances the chaperone activity of Hsp90 (an ATPase known to associate with PGK1), activating multi-stress resistance. This was established by enzymology and X-ray crystallography. X-ray crystallography, enzymatic activity assays, binding assays, Hsp90 ATPase assays, rodent stroke/sepsis models Nature chemical biology High 25383758
2022 PGK1 acts as a protein kinase to phosphorylate PRAS40 at threonine 246 under normoxia, suppressing autophagy-mediated cell death and promoting cell proliferation. Under hypoxia, PGK1 binding switches from PRAS40 to Beclin1, increasing Beclin1 phosphorylation and inducing autophagy. Co-IP, in vitro kinase assay, site-directed mutagenesis, autophagy assays, xenograft model Cell death & disease Medium 35058442
2024 PRMT1-mediated asymmetric dimethylation of PGK1 at arginine 206 (R206) enhances phosphorylation of PGK1 at S203, which inhibits mitochondrial function and promotes glycolysis in colorectal cancer cells. Mass spectrometry, site-directed mutagenesis, Co-IP, glycolysis assays, western blot with modification-specific antibodies, human tissue correlation Cell death & disease Medium 38402202
2024 PGK1 is succinylated at K191 and K192 by succinate generated via P4HA1, a process regulated by HIF1α/ATF3 transcriptional control of P4HA1. Succinylation at these sites inhibits proteasomal degradation of PGK1, increasing aerobic glycolysis and lactate production in glioblastoma. ChIP assay, LC-MS/MS, in vitro succinate production assays, Seahorse metabolic assay, site-directed mutagenesis, intracranial mouse model Neuro-oncology Medium 38441561
2024 Hypoxia decreases PGK1 crotonylation (Kcr) at K131, K156, and K220 via upregulation of ECHS1, which interacts with PGK1. Abolishment of PGK1 Kcr promotes glycolysis and suppresses mitochondrial pyruvate metabolism by activating PDHK1. Quantitative proteomics (crotonylome analysis), Co-IP, site-directed mutagenesis, metabolic assays, western blot Nature communications Medium 39134530
2019 Nuclear PGK1 preferentially drives cell metastasis via mitochondrial oxidative phosphorylation induction in SMAD4-negative pancreatic cancer cells, whereas cytoplasmic PGK1 supports proliferation through its glycolytic enzyme function. SMAD4 represses PGK1 transcription via TGF-β/SMAD4 signaling as demonstrated by luciferase reporter and ChIP assays. Dual luciferase reporter assay, ChIP, subcellular fractionation, metabolomics, proliferative and metastatic assays, xenograft model Gut Medium 31611300
2022 KIF15 promotes PGK1 stability by recruiting deubiquitinase USP10 to PGK1, enhancing USP10-mediated deubiquitination of PGK1. KIF15 binds both PGK1 and USP10 through its coil2 domain, as determined by truncation analysis and Co-IP/MS. Co-IP, mass spectrometry, ubiquitination assay, KIF15 truncation constructs, glycolysis assays, xenograft model Cell death & disease Medium 36807568
2020 PGK1 inhibition by the small molecule CBR-470-1 leads to methylglyoxal modification of Keap1, causing Keap1-Nrf2 disassociation and activation of the Nrf2 antioxidant cascade. PGK1 depletion or knockout mimics this effect, establishing PGK1 as an upstream regulator of the Keap1-Nrf2 pathway. PGK1 inhibitor treatment, CRISPR/Cas9 KO, shRNA knockdown, Nrf2 reporter assays, Keap1 modification analysis, cell viability assays Aging Medium 32649311
2022 DC-PGKI, an ATP-competitive PGK1 inhibitor, suppresses both glycolytic activity and kinase function of PGK1. Inhibition of PGK1 causes NRF2 accumulation, nuclear translocation, and binding to the Il-1β and Il-6 gene promoter regions, inhibiting LPS-induced expression of these cytokines in macrophages. High-throughput screen, binding affinity measurement (Kd), thermal shift assay, glycolysis assays, ELISA for cytokines, ChIP for NRF2 binding, DSS colitis mouse model Acta pharmaceutica Sinica. B Medium 36386479
2019 Extracellular PGK1 promotes neurite outgrowth of motoneurons independently of the Nogo66/NgR pathway by triggering reduction of p-Cofilin-S3 (a growth cone collapse marker) through decreasing Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 signaling. NogoA-overexpressing muscle cells reduce PGK1 secretion, linking extracellular PGK1 to muscle-nerve signaling. Recombinant Pgk1 supplementation, pathway inhibitor studies, zebrafish NogoA overexpression model, SOD1 G93A mouse model injection, signaling cascade analysis by western blot eLife Medium 31361595
2023 Extracellular PGK1 interacts specifically with neural membrane Enolase-2 (ENE2) via PGK1 residues 325–417 binding to ENE2 residues 405–431. This interaction promotes motoneuron neurite outgrowth by reducing p-P38-T180/p-Limk1-S323/p-Cofilin signaling. Recombinant protein binding (immunoelectron microscopy), domain truncation assays, Co-IP/pulldown, signaling cascade western blot, neurite outgrowth assay Communications biology Medium 37582937
2020 PGK1 interacts with androgen receptor (AR) in granulosa cells and inhibits AR ubiquitination in an E3 ligase SKP2-dependent manner, increasing AR protein stability and promoting its nuclear translocation. This regulates expression of ovulation-related genes. Co-IP, GST pulldown, co-localization, ubiquitination assay, RNA-seq, pharmaceutical rescue in PCOS mouse model EBioMedicine Medium 33096483
2019 PGK1 directly interacts with HSP90, and the ATP generated from PGK1 modulates the ATPase activity of HSP90, contributing to cisplatin chemoresistance in endometrial cancer through HSP90/ERK-mediated DNA repair and methylation. Co-immunoprecipitation, western blot for HSP90/ERK/DNA repair pathway proteins, PGK1 shRNA knockdown, cell viability assays Molecular medicine (Cambridge, Mass.) Low 30925862
2021 PGK1 interacts with and stabilizes GSK3β through Hsp90 coupling. PGK1 interacts with the C-terminal domain of Hsp90α, facilitating GSK3β-Hsp90 binding (despite Hsp90 not directly binding GSK3β). This stabilization of GSK3β is ATP-dependent and maintains Wnt/β-catenin pathway suppression, regulating breast cancer stem cell stemness. Co-IP and mass spectral assay, bacterially purified protein binding assays, Hsp90α domain/mutant constructs, western blot for GSK3β stability, mammosphere assays Cancer biology & medicine Medium 34403222
2020 PGK1 perturbation (siRNA knockdown) in five cancer cell lines has no effect or only marginal effects on glucose consumption and lactate production; PGK1 knockdown increases concentrations of glycolytic intermediates upstream (fructose 1,6-bisphosphate, DHAP, G3P, 1,3-BPG) without substantially altering glycolytic flux. The Km for 1,3-BPG (forward substrate) was determined as 6.86 μM for human PGK1 and for 3-PG as 186 μM. Enzymatic kinetic assay (developed forward reaction assay), siRNA knockdown in 5 cancer cell lines, cell-free glycolysis system with PGK1 titration, metabolite measurement The Journal of biological chemistry High 32217690
2023 PGK1 interacts with NLRP3 in macrophages; LPS stimulation enhances the PGK1-NLRP3 interaction both in vivo and in vitro. PGK1 phosphorylates NLRP3, and absence of PGK1 reduces NLRP3 phosphorylation, inhibiting macrophage pyroptosis and M1 polarization in acute lung injury. Co-IP, western blot for NLRP3 phosphorylation, siRNA knockdown of PGK1 in BMDMs, LPS-induced ALI mouse model, PGK1 inhibitor NG52 Respiratory research Medium 39080660
2009 In yeast S. cerevisiae, overexpression of PGK1 (glycolytic phosphoglycerate kinase) suppresses apoptotic phenotypes including abnormal aging, oxidative stress sensitivity, and nuclear integrity defects in an lsm4 mutant strain. Multicopy suppressor screen, yeast genetic assay, oxidative stress resistance assay Yeast (Chichester, England) Low 19180641
2023 PGK1 inhibition by CBR-470-1 or genetic depletion leads to Keap1 methylglyoxal modification, activating Nrf2 signaling and reducing protein aggregation. TZ activation of Pgk1 increases intracellular ATP, which reduces pathological condensate density (FUS-P525L-GFP) and enhances Hsp90 interaction with ULK1 to promote autophagy-mediated clearance in models of neurodegeneration. Primary neuron culture, protein aggregate imaging, Hsp90 Co-IP with ULK1, ATP measurement, Drosophila tau model, APP/PS1 mouse model, MSA rat model with alpha-synuclein Molecular neurobiology Medium 37249790
2023 PGK1 interacts with ITI-H4 and blocks KLKB1-mediated cleavage of ITI-H4. PGK1 also inhibits pro-inflammatory signaling by inhibiting the JAK2/STAT3 pathway. Co-immunoprecipitation, MALDI-TOF/MS, cleavage assay, western blot for JAK2/STAT3 phosphorylation Biomedicine & pharmacotherapy Low 36841032
2009 PGK1 secreted by prostate cancer cells induces osteoblastic differentiation of bone marrow stromal cells and inhibits osteoclastogenesis, promoting bone formation at metastatic sites. PGK1 overexpression in PCa cell lines, in vivo bone metastasis model, osteoblast/osteoclast differentiation assays Molecular cancer research : MCR Low 19825988
2023 PTBP1 promotes PGK1 mRNA stability by directly binding to PGK1 mRNA, increasing PGK1 protein levels. Elevated PGK1 activates the PGK1/SNAIL axis to promote gastric cancer cell migration. RIP assay demonstrating PTBP1 binding to PGK1 mRNA, mRNA stability assay, western blot, knockdown/overexpression, liver metastasis mouse model Cells Low 38247832

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis. Molecular cell 413 26942675
1987 Cloning and expression of the mouse pgk-1 gene and the nucleotide sequence of its promoter. Gene 350 3440520
1995 Turnover mechanisms of the stable yeast PGK1 mRNA. Molecular and cellular biology 282 7891709
2020 O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth. Nature communications 281 31911580
2018 Macrophage-Associated PGK1 Phosphorylation Promotes Aerobic Glycolysis and Tumorigenesis. Molecular cell 267 30029001
2016 Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis. Hepatology (Baltimore, Md.) 231 27774669
2019 PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1. Molecular cell 178 31492635
2017 MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway. Cancer research 158 28923857
2019 PGK1-mediated cancer progression and drug resistance. American journal of cancer research 133 31815035
2019 Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer. Gut 130 31611300
2014 Terazosin activates Pgk1 and Hsp90 to promote stress resistance. Nature chemical biology 125 25383758
1994 DNA repair rates mapped along the human PGK1 gene at nucleotide resolution. Science (New York, N.Y.) 123 8128226
1977 Electrophoretic variation for x-chromosome-linked phosphoglycerate kinase (pgk-1) in the mouse. Genetics 121 17248765
2021 FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect. Molecular therapy : the journal of the American Society of Gene Therapy 111 33940159
2017 Protein kinase activity of the glycolytic enzyme PGK1 regulates autophagy to promote tumorigenesis. Autophagy 96 28486006
2015 Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1. PLoS biology 84 26356530
2002 Overexpression of human phosphoglycerate kinase 1 (PGK1) induces a multidrug resistance phenotype. Anticancer research 79 12174867
2022 PGK1 contributes to tumorigenesis and sorafenib resistance of renal clear cell carcinoma via activating CXCR4/ERK signaling pathway and accelerating glycolysis. Cell death & disease 74 35121728
2020 Phosphoglycerate kinase 1 (PGK1) in cancer: A promising target for diagnosis and therapy. Life sciences 74 32479953
2011 FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 73 21471709
2018 PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α-Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 71 30537744
2022 LncRNA NEAT1 facilitates glioma progression via stabilizing PGK1. Journal of translational medicine 67 35123484
2017 PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process. International journal of molecular sciences 65 28749413
2018 Nuclear PGK1 Alleviates ADP-Dependent Inhibition of CDC7 to Promote DNA Replication. Molecular cell 61 30392930
2023 mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs. Nature communications 59 36849569
1994 Murine PGK-1 promoter drives widespread but not uniform expression in transgenic mice. Developmental dynamics : an official publication of the American Association of Anatomists 58 7994075
2008 PGK1 a potential marker for peritoneal dissemination in gastric cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 55 18453750
2024 PRMT1-mediated PGK1 arginine methylation promotes colorectal cancer glycolysis and tumorigenesis. Cell death & disease 49 38402202
2024 Hypoxia-induced downregulation of PGK1 crotonylation promotes tumorigenesis by coordinating glycolysis and the TCA cycle. Nature communications 49 39134530
2020 Novel PGK1 determines SKP2-dependent AR stability and reprograms granular cell glucose metabolism facilitating ovulation dysfunction. EBioMedicine 49 33096483
2017 Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis. Cancer chemotherapy and pharmacology 49 28391351
2020 Activation of PGK1 under hypoxic conditions promotes glycolysis and increases stem cell‑like properties and the epithelial‑mesenchymal transition in oral squamous cell carcinoma cells via the AKT signalling pathway. International journal of oncology 48 32705252
2024 HIF1α/ATF3 partake in PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma. Neuro-oncology 46 38441561
2019 PGK1 facilities cisplatin chemoresistance by triggering HSP90/ERK pathway mediated DNA repair and methylation in endometrial endometrioid adenocarcinoma. Molecular medicine (Cambridge, Mass.) 46 30925862
1992 The gene responsible for X-linked cleft palate (CPX) in a British Columbia native kindred is localized between PGK1 and DXYS1. American journal of human genetics 46 1570839
2019 ACTL6A regulates follicle-stimulating hormone-driven glycolysis in ovarian cancer cells via PGK1. Cell death & disease 44 31649264
2012 Glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPARγ in breast cancer pathophysiology. Journal of drug targeting 44 23130662
2020 MicroRNA-16-1-3p Represses Breast Tumor Growth and Metastasis by Inhibiting PGK1-Mediated Warburg Effect. Frontiers in cell and developmental biology 43 33344462
2016 PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 43 27342824
1994 Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3. Human molecular genetics 41 8162050
2019 PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone. Cell death & disease 39 31767834
2022 LncRNA HCG18 promotes osteosarcoma growth by enhanced aerobic glycolysis via the miR-365a-3p/PGK1 axis. Cellular & molecular biology letters 37 34991445
2020 GBP1 promotes erlotinib resistance via PGK1‑activated EMT signaling in non‑small cell lung cancer. International journal of oncology 37 32582960
2017 Co-opting ATP-generating glycolytic enzyme PGK1 phosphoglycerate kinase facilitates the assembly of viral replicase complexes. PLoS pathogens 37 29059239
2023 The Role of PGK1 in Promoting Ischemia/Reperfusion Injury-Induced Microglial M1 Polarization and Inflammation by Regulating Glycolysis. Neuromolecular medicine 36 36749430
2022 Therapeutic inhibition of PPARα-HIF1α-PGK1 signaling targets leukemia stem and progenitor cells in acute myeloid leukemia. Cancer letters 36 36396101
2022 A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1β and IL-6. Acta pharmaceutica Sinica. B 35 36386479
2019 miR-548c-5p inhibits colorectal cancer cell proliferation by targeting PGK1. Journal of cellular physiology 35 30932211
2022 PGK1 represses autophagy-mediated cell death to promote the proliferation of liver cancer cells by phosphorylating PRAS40. Cell death & disease 33 35058442
2020 MiRNA-215-5p alleviates the metastasis of prostate cancer by targeting PGK1. European review for medical and pharmacological sciences 32 32017004
2022 Evodiamine prevents traumatic brain injury through inhibiting oxidative stress via PGK1/NRF2 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 36076551
2019 Parkinsonism in PGK1 deficiency implicates the glycolytic pathway in nigrostriatal dysfunction. Parkinsonism & related disorders 30 30975619
2022 A novel inhibitor of PGK1 suppresses the aerobic glycolysis and proliferation of hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 36516697
2009 PGK1, the gene encoding the glycolitic enzyme phosphoglycerate kinase, acts as a multicopy suppressor of apoptotic phenotypes in S. cerevisiae. Yeast (Chichester, England) 29 19180641
2021 lncRNA SNHG26 promoted the growth, metastasis, and cisplatin resistance of tongue squamous cell carcinoma through PGK1/Akt/mTOR signal pathway. Molecular therapy oncolytics 28 35118193
2020 Perturbation of phosphoglycerate kinase 1 (PGK1) only marginally affects glycolysis in cancer cells. The Journal of biological chemistry 27 32217690
2005 Molecular characterization of the 3-phosphoglycerate kinase gene (PGK1) from the methylotrophic yeast Pichia pastoris. Yeast (Chichester, England) 27 16034819
2023 KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer. Cell death & disease 26 36807568
2024 Glycolytic enzyme PGK1 promotes M1 macrophage polarization and induces pyroptosis of acute lung injury via regulation of NLRP3. Respiratory research 25 39080660
2015 Metabolic alteration--Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics. International journal of surgery (London, England) 25 26298000
2009 Expression of PGK1 by prostate cancer cells induces bone formation. Molecular cancer research : MCR 25 19825988
1991 Timing of paternal Pgk-1 expression in embryos of transgenic mice. Development (Cambridge, England) 25 1879353
2021 PTCSC3-mediated glycolysis suppresses thyroid cancer progression via interfering with PGK1 degradation. Journal of cellular and molecular medicine 24 34337858
2023 Activation of Pgk1 Results in Reduced Protein Aggregation in Diverse Neurodegenerative Conditions. Molecular neurobiology 23 37249790
2022 PGK1 : An Essential Player in Modulating Tumor Metabolism. Methods in molecular biology (Clifton, N.J.) 23 34473315
2022 Rutaecarpine Attenuates Oxidative Stress-Induced Traumatic Brain Injury and Reduces Secondary Injury via the PGK1/KEAP1/NRF2 Signaling Pathway. Frontiers in pharmacology 23 35529443
2019 Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA. eLife 23 31361595
2021 Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders. International journal of molecular sciences 22 35008842
2020 Identification of a novel non-ATP-competitive protein kinase inhibitor of PGK1 from marine nature products. Biochemical pharmacology 21 33212041
2012 Evolutionary dynamics of the Pgk1 gene in the polyploid genus Kengyilia (Triticeae: Poaceae) and its diploid relatives. PloS one 21 22363562
2024 Novel inhibitors targeting the PGK1 metabolic enzyme in glycolysis exhibit effective antitumor activity against kidney renal clear cell carcinoma in vitro and in vivo. European journal of medicinal chemistry 20 38354523
2022 N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability. Journal of cancer research and clinical oncology 20 36171455
2017 17beta-hydroxysteroid dehydrogenase type 5 is negatively correlated to apoptosis inhibitor GRP78 and tumor-secreted protein PGK1, and modulates breast cancer cell viability and proliferation. The Journal of steroid biochemistry and molecular biology 20 28457968
2013 PGK1 as predictor of CXCR4 expression, bone marrow metastases and survival in neuroblastoma. PloS one 18 24376734
2022 Blockade of PGK1 and ALDOA enhances bilirubin control of Th17 cells in Crohn's disease. Communications biology 17 36131123
2021 Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer. Frontiers in oncology 17 33747900
2020 PGK1 inhibitor CBR-470-1 protects neuronal cells from MPP+. Aging 17 32649311
2024 TRIM50 inhibits glycolysis and the malignant progression of gastric cancer by ubiquitinating PGK1. International journal of biological sciences 16 38993561
2021 PGK1-coupled HSP90 stabilizes GSK3β expression to regulate the stemness of breast cancer stem cells. Cancer biology & medicine 16 34403222
2018 Rab11-FIP2 suppressed tumor growth via regulation of PGK1 ubiquitination in non-small cell lung cancer. Biochemical and biophysical research communications 16 30471866
2013 Protein Stability, Folding and Misfolding in Human PGK1 Deficiency. Biomolecules 16 24970202
2024 Albiflorin alleviates neuroinflammation of rats after MCAO via PGK1/Nrf2/HO-1 signaling pathway. International immunopharmacology 15 38870884
2021 HPV16 E6/E7 stabilize PGK1 protein by reducing its poly-ubiquitination in cervical cancer. Cell biology international 15 34882921
2007 Altered expression of PGK1 in a family with phosphoglycerate kinase deficiency. Muscle & nerve 15 17661373
1991 Promoter structure and expression of the 3-phosphoglycerate kinase-encoding gene (pgk1) of Trichoderma reesei. Gene 15 1937034
2023 Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 14 37557014
2023 SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma. Journal of experimental & clinical cancer research : CR 14 38098044
2024 CircGLIS3 promotes gastric cancer progression by regulating the miR-1343-3p/PGK1 pathway and inhibiting vimentin phosphorylation. Journal of translational medicine 13 38459513
2023 Targeting the Glycolytic Enzyme PGK1 to Inhibit the Warburg Effect: A New Strategy for Keloid Therapy. Plastic and reconstructive surgery 13 36728674
2023 PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 13 36841032
2023 Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons. Communications biology 13 37582937
2023 Downregulation of pro-surfactant protein B contributes to the recurrence of early-stage non-small cell lung cancer by activating PGK1-mediated Akt signaling. Experimental hematology & oncology 13 37946295
2020 miR-6869-5p Inhibits Glioma Cell Proliferation and Invasion via Targeting PGK1. Mediators of inflammation 13 32565733
2015 A constitutive expression system for Pichia pastoris based on the PGK1 promoter. Biotechnology letters 13 26585331
2024 The oncogenic role and regulatory mechanism of PGK1 in human non-small cell lung cancer. Biology direct 12 38163864
2022 Circ_0076305 facilitates prostate cancer development via sponging miR-411-5p and regulating PGK1. Andrologia 12 35238066
2022 Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1. Clinical & experimental metastasis 12 35715622
2023 Intervention of Tanshinone IIA on the PGK1-PDHK1 Pathway to Reprogram Macrophage Phenotype After Myocardial Infarction. Cardiovascular drugs and therapy 11 37991600
2022 The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents. Frontiers in pharmacology 11 35387336
2024 RNA Binding Protein PTBP1 Promotes the Metastasis of Gastric Cancer by Stabilizing PGK1 mRNA. Cells 10 38247832

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