Affinage

PGK1

Phosphoglycerate kinase 1 · UniProt P00558

Length
417 aa
Mass
44.6 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PGK1 is a glycolytic kinase that catalyzes the transfer of a phosphoryl group from 1,3-bisphosphoglycerate to ADP, generating ATP and 3-phosphoglycerate, but also functions as a regulated protein kinase with non-canonical substrates including PDHK1, Beclin1, PRAS40, and NLRP3. Its glycolytic activity is modulated by phosphorylation (T243 by PDPK1, Y324 autophosphorylation dephosphorylated by PTEN), acetylation (K220 inhibitory via KAT9/HDAC3, K323 activating via PCAF/SIRT7), crotonylation (K131/K156/K220, inhibitory), succinylation (K191/K192, stabilizing), and O-GlcNAcylation (T255, activating), while ERK-mediated S203 phosphorylation and PIN1 isomerization trigger its mitochondrial translocation where it phosphorylates PDHK1 at T338 to suppress pyruvate oxidation, and K388 acetylation by NAA10 enables its phosphorylation of Beclin1 at S30 to initiate autophagy (PMID:26942675, PMID:31911580, PMID:30029001, PMID:26356530, PMID:27774669, PMID:28486006, PMID:31492635). PGK1 also localizes to the nucleus where CK2α-dependent S256 phosphorylation promotes its interaction with CDC7, coupling local ATP regeneration to relief of ADP-mediated inhibition of the CDC7–ASK replication initiation complex (PMID:30392930). Beyond intracellular roles, PGK1 associates with Hsp90 to stabilize client proteins such as GSK3β and ULK1, and extracellular PGK1 engages neuronal membrane Enolase-2 to promote neurite outgrowth (PMID:34403222, PMID:37249790, PMID:37582937).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2008 Low

    An initial observation that PGK1 forms a complex with GAPDH in developing tissue raised the question of whether PGK1 participates in higher-order glycolytic assemblies, but provided no functional insight.

    Evidence Co-IP/western blot in mouse tooth germ

    PMID:18228199

    Open questions at the time
    • No functional follow-up of the PGK1–GAPDH complex
    • Single co-IP without reciprocal validation
    • No evidence this complex has catalytic or regulatory significance
  2. 2014 High

    Structural and functional characterization of terazosin binding to PGK1 established that small molecules can allosterically activate PGK1, and that the resulting ATP fuels Hsp90 chaperone activity—revealing a functional PGK1–Hsp90 axis beyond canonical glycolysis.

    Evidence X-ray crystallography of terazosin–PGK1 complex, enzymology, co-IP, rodent disease models

    PMID:25383758

    Open questions at the time
    • Structural basis of PGK1–Hsp90 interaction not resolved
    • Whether endogenous ligands mimic terazosin activation unknown
  3. 2015 High

    Identification of K220 acetylation (written by KAT9, erased by HDAC3) as a switch that inhibits PGK1 by disrupting ADP binding established that post-translational modifications directly tune glycolytic activity, and linked this regulation to insulin/PI3K/AKT/mTOR signaling.

    Evidence Co-IP, enzymatic activity assays, mutagenesis, kinase assays

    PMID:26356530

    Open questions at the time
    • Whether K220 acetylation affects PGK1 protein kinase function not tested
    • Interplay between K220 acetylation and other PTMs at nearby sites not addressed
  4. 2016 High

    Two studies revealed that PGK1 functions as a protein kinase beyond its glycolytic role: ERK-dependent S203 phosphorylation triggers mitochondrial translocation where PGK1 phosphorylates PDHK1 at T338 to suppress pyruvate oxidation, while K323 acetylation by PCAF (reversed by SIRT7) enhances catalytic activity in liver cancer cells.

    Evidence In vitro kinase assays, mass spectrometry, mutagenesis, xenograft models (for S203/PDHK1); co-IP, enzymatic assays, mutagenesis (for K323)

    PMID:26942675 PMID:27774669

    Open questions at the time
    • Whether PDHK1 phosphorylation by PGK1 occurs in non-cancer tissues unknown
    • Structural basis of PGK1's dual kinase specificity (metabolite vs. protein substrates) not resolved
  5. 2017 High

    Discovery that K388 acetylation by NAA10 enables PGK1 to phosphorylate Beclin1 at S30 under nutrient stress established PGK1 as a direct upstream activator of VPS34-dependent autophagy initiation, connecting metabolic sensing to autophagosome biogenesis.

    Evidence In vitro kinase assays, co-IP, mutagenesis, brain tumor models

    PMID:28486006

    Open questions at the time
    • Whether PGK1-Beclin1 phosphorylation occurs in non-tumor contexts not established
    • Mechanism by which K388 acetylation specifically licenses protein kinase activity unclear
  6. 2018 High

    Two advances deepened understanding of PGK1 regulation and nuclear function: PDPK1-mediated T243 phosphorylation alters substrate affinity to accelerate glycolysis, and CK2α-mediated S256 phosphorylation enables nuclear PGK1 to interact with CDC7, regenerating ATP locally to relieve ADP-dependent allosteric inhibition of CDC7–ASK and promote DNA replication initiation.

    Evidence In vitro kinase assays, mutagenesis, DNA replication assays, xenograft models

    PMID:30029001 PMID:30392930

    Open questions at the time
    • Whether nuclear PGK1–CDC7 coupling is essential for normal S-phase progression outside oncogenic contexts not tested
    • How T243 and S256 phosphorylation are coordinated is unknown
  7. 2019 High

    Identification of Y324 autophosphorylation as the activating event for PGK1's protein kinase function—and PTEN as its direct phosphatase—established a tumor-suppressor checkpoint governing PGK1's non-canonical activity, with Y324F knockin mice showing impaired brain tumor growth.

    Evidence In vitro phosphatase assays, co-IP, mutagenesis, knockin mouse models, GBM specimens

    PMID:31492635

    Open questions at the time
    • Whether other phosphatases also target Y324 unknown
    • Structural mechanism of intermolecular autophosphorylation not resolved
  8. 2020 High

    Multiple studies refined PGK1's regulatory landscape and kinetic properties: O-GlcNAcylation at T255 was shown to simultaneously activate glycolytic activity and induce mitochondrial translocation; rigorous enzyme kinetics revealed that despite high catalytic efficiency, PGK1 perturbation has marginal effects on overall glycolytic flux; PGK1 inhibition was linked to methylglyoxal-mediated Keap1 modification and Nrf2 activation; and PGK1 was found to stabilize the androgen receptor via SKP2-dependent suppression of ubiquitination.

    Evidence Mass spectrometry/mutagenesis/xenografts (T255); cell-free glycolysis reconstitution (kinetics); CRISPR/shRNA/reporter assays (Nrf2); co-IP/GST pull-down/ubiquitination assays (AR)

    PMID:31911580 PMID:32217690 PMID:32649311 PMID:33096483

    Open questions at the time
    • How O-GlcNAcylation mechanistically alters mitochondrial targeting is unknown
    • Whether marginal flux impact applies to all tissue types needs clarification
    • AR stabilization mechanism not independently replicated
  9. 2021 Medium

    Mapping the PGK1–Hsp90 interaction to Hsp90's C-terminal domain showed that PGK1 facilitates GSK3β client loading into Hsp90's closed conformation, linking PGK1 to chaperone-dependent protein homeostasis and cancer stemness.

    Evidence Co-IP, purified protein binding, Hsp90 domain mutants, mammosphere assays

    PMID:34403222

    Open questions at the time
    • Whether PGK1–Hsp90 coupling is specific to GSK3β or generalizes to other clients not established
    • Single lab observation
  10. 2022 Medium

    PGK1's protein kinase activity was extended to PRAS40 (T246) under normoxia and NLRP3 under inflammation, while PGK1 activation by terazosin was shown to promote Hsp90–ULK1-dependent autophagy for aggregate clearance in neurodegeneration models, and an ATP-competitive inhibitor (DC-PGKI) confirmed PGK1's role in NRF2-dependent anti-inflammatory cytokine regulation.

    Evidence In vitro kinase assays, co-IP, xenograft models (PRAS40/NLRP3); pharmacological activation in neuron cultures and disease animal models (terazosin/Hsp90/ULK1); HTS, ChIP, colitis model (DC-PGKI/NRF2)

    PMID:35058442 PMID:36386479 PMID:37249790 PMID:39080660

    Open questions at the time
    • NLRP3 phosphorylation site not mapped
    • Physiological relevance of oxygen-dependent PRAS40/Beclin1 substrate switching requires independent validation
    • Whether PGK1–ULK1 coupling is direct or entirely Hsp90-mediated not resolved
  11. 2023 Medium

    Extracellular PGK1 was shown to directly engage neuronal Enolase-2 through mapped domains (PGK1 325-417; ENO2 405-431), suppressing p38/Limk1/Cofilin signaling and promoting neurite outgrowth—establishing a non-enzymatic, extracellular signaling role for PGK1. Separately, mcPGK1 (a mitochondria-encoded circRNA) was found to facilitate PGK1 mitochondrial import via TOM40.

    Evidence Co-IP, immunoelectron microscopy, domain truncation, neurite assays (ENO2); co-IP, fractionation, xenograft/sphere assays (mcPGK1/TOM40)

    PMID:36807568 PMID:37582937

    Open questions at the time
    • Source and regulation of extracellular PGK1 release not determined
    • Whether mcPGK1 acts as a chaperone or import scaffold is unclear
    • ENO2 interaction not validated in vivo
  12. 2024 Medium

    Additional PTM layers were discovered: PRMT1-mediated R206 dimethylation primes S203 phosphorylation to promote glycolysis; ECHS1-dependent reduction of lysine crotonylation at K131/K156/K220 under hypoxia activates PDHK1 signaling; and P4HA1/succinate-driven succinylation at K191/K192 stabilizes PGK1 protein levels.

    Evidence Mass spectrometry, mutagenesis, Seahorse assays, xenograft/intracranial models

    PMID:38402202 PMID:38441561 PMID:39134530

    Open questions at the time
    • Crosstalk hierarchy among methylation, crotonylation, acetylation, and phosphorylation at overlapping sites not mapped
    • Whether succinylation-mediated stabilization is specific to glioblastoma unknown
    • Writers and erasers for crotonylation and succinylation marks not fully identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis for PGK1's dual specificity as a metabolite kinase and protein kinase, the integrated PTM code that controls substrate switching and subcellular targeting, and whether PGK1's protein kinase activity contributes to normal physiology beyond cancer and neurodegeneration.
  • No crystal structure of PGK1 bound to a protein substrate
  • No systematic mapping of PTM crosstalk hierarchy
  • Physiological relevance of protein kinase function in normal (non-disease) tissues largely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 9 GO:0140096 catalytic activity, acting on a protein 5 GO:0140657 ATP-dependent activity 4 GO:0044183 protein folding chaperone 2
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005576 extracellular region 1
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2 R-HSA-69306 DNA Replication 1
Complex memberships
PGK1–Hsp90

Evidence

Reading pass · 26 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 phosphorylation of PGK1 at S203, 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, reducing ROS, increasing lactate production, and promoting tumorigenesis. In vitro kinase assays, mass spectrometry, co-immunoprecipitation, subcellular fractionation, mutagenesis, xenograft tumor models Molecular cell High 26942675
2020 PGK1 is O-GlcNAcylated at threonine 255 (T255); this modification activates PGK1 glycolytic activity to enhance lactate production and simultaneously induces PGK1 translocation into mitochondria, where it acts as a kinase to inhibit the pyruvate dehydrogenase (PDH) complex and reduce oxidative phosphorylation. Blocking T255 O-GlcNAcylation decreases colon cancer cell proliferation and tumor growth. Mass spectrometry, site-directed mutagenesis, subcellular fractionation, in vitro kinase assays, xenograft models Nature communications High 31911580
2018 M2 macrophage-derived IL-6 activates PDPK1, which phosphorylates PGK1 at threonine 243 (T243). This phosphorylation alters substrate affinity and facilitates the PGK1-catalyzed reaction toward glycolysis, promoting aerobic glycolysis, tumor cell proliferation, and tumorigenesis. In vitro kinase assays, co-immunoprecipitation, mutagenesis, IL-6 neutralization, xenograft tumor models Molecular cell High 30029001
2016 PGK1 is acetylated at K323 by the acetyltransferase PCAF, which enhances its enzymatic activity and promotes cancer cell metabolism. SIRT7 acts as the deacetylase that removes this acetylation mark. K323 acetylation is an important regulatory mechanism for PGK1 activity in liver cancer cells. Mass spectrometry, co-immunoprecipitation, enzymatic activity assays, mutagenesis, loss-of-function studies Hepatology (Baltimore, Md.) High 27774669
2015 PGK1 is acetylated at lysine 220 (K220) by KAT9, which inhibits PGK1 activity by disrupting ADP substrate binding. HDAC3 deacetylates K220 to activate PGK1. Insulin promotes K220 deacetylation through the PI3K/AKT/mTOR pathway, which phosphorylates HDAC3 at S424, promoting HDAC3-PGK1 interaction and PGK1 deacetylation. Co-immunoprecipitation, enzymatic activity assays, mutagenesis, kinase assays, cell-based metabolic assays PLoS biology High 26356530
2019 PTEN directly interacts with PGK1 and dephosphorylates PGK1 at Y324. PGK1 undergoes intermolecular autophosphorylation at Y324, which activates it as a protein kinase. PTEN's protein phosphatase activity inhibits this autophosphorylation, thereby suppressing glycolysis, ATP production, and brain tumor cell proliferation. Knockin of PGK1 Y324F inhibits brain tumor formation. In vitro phosphatase assays, co-immunoprecipitation, mutagenesis, knockin mouse models, glioblastoma specimens Molecular cell High 31492635
2017 Under glutamine deprivation or hypoxia, PGK1 is acetylated at K388 by NAA10/ARD1 in an mTOR-inhibition-dependent manner. Acetylated PGK1 interacts with and phosphorylates BECN1/Beclin1 at S30, which enhances ATG14-associated PIK3C3/VPS34-BECN1-PIK3R4/VPS15 complex activity, increasing phosphatidylinositol-3-phosphate generation and initiating autophagy. Co-immunoprecipitation, in vitro kinase assays, mutagenesis, loss-of-function studies, brain tumor models Autophagy High 28486006
2018 EGFR- and ERK-activated casein kinase 2α (CK2α) phosphorylates nuclear PGK1 at S256, causing PGK1 to interact with CDC7. CDC7-bound PGK1 converts ADP (generated from CDC7-mediated MCM phosphorylation) to ATP, relieving ADP-dependent allosteric inhibition of the CDC7-ASK complex and thereby promoting DNA replication initiation, cell proliferation, and tumorigenesis. Co-immunoprecipitation, in vitro kinase/ATPase assays, mutagenesis, DNA replication assays, tumor xenograft models Molecular cell High 30392930
2014 Terazosin binds phosphoglycerate kinase 1 (Pgk1) at a site distinct from its α1-adrenergic receptor target, activating Pgk1 enzymatic activity likely by promoting ATP release. The ATP generated by Pgk1 enhances the ATPase/chaperone activity of Hsp90, which associates with Pgk1 and promotes multi-stress resistance. X-ray crystallography confirmed the terazosin-Pgk1 binding site. X-ray crystallography, enzymology assays, co-immunoprecipitation, rodent stroke and sepsis models Nature chemical biology High 25383758
2022 PGK1 directly interacts with BECN1 and, under normoxia, phosphorylates PRAS40 at threonine 246, suppressing autophagy-mediated cell death and promoting liver cancer cell proliferation. Under hypoxia, PGK1 binding switches from PRAS40 to Beclin1, increasing Beclin1 phosphorylation and inducing autophagy. Co-immunoprecipitation, in vitro kinase assays, mutagenesis, xenograft tumor models Cell death & disease Medium 35058442
2024 PRMT1 mediates asymmetric dimethylation of PGK1 at arginine 206 (R206), which enhances subsequent phosphorylation of PGK1 at S203, inhibiting mitochondrial function and promoting glycolysis in colorectal cancer cells. Mass spectrometry, co-immunoprecipitation, mutagenesis, enzymatic assays, patient tissue analysis Cell death & disease Medium 38402202
2024 ECHS1 is upregulated under hypoxia and interacts with PGK1, leading to downregulation of PGK1 lysine crotonylation (Kcr) at K131, K156, and K220. Abolishment of PGK1 Kcr promotes glycolysis and suppresses mitochondrial pyruvate metabolism by activating PDHK1, coordinating glycolysis and the TCA cycle. Quantitative proteomics, co-immunoprecipitation, mutagenesis, Seahorse metabolic assays, xenograft models Nature communications Medium 39134530
2024 HIF1α and ATF3 regulate P4HA1 transcription in opposing directions, altering succinate production. Elevated succinate leads to succinylation of PGK1 at K191 and K192 via P4HA1/succinate signaling, inhibiting proteasomal degradation of PGK1 and significantly increasing aerobic glycolysis (lactate generation) in glioblastoma. ChIP assays, LC-MS/MS, in vitro succinate production assays, Seahorse assay, intracranial mouse models Neuro-oncology Medium 38441561
2022 PGK1 directly interacts with NLRP3 and phosphorylates NLRP3 upon LPS stimulation; loss of PGK1 reduces NLRP3 phosphorylation and inhibits macrophage pyroptosis and M1 polarization in acute lung injury. Co-immunoprecipitation, in vitro kinase assays, siRNA knockdown, mouse ALI models Respiratory research Medium 39080660
2019 In SMAD4-negative pancreatic cancer, TGF-β/SMAD4 represses PGK1 transcription. Nuclear PGK1 preferentially drives cell metastasis via induction of mitochondrial oxidative phosphorylation, whereas cytoplasmic PGK1 supports proliferation by functioning as a glycolytic enzyme, demonstrating that PGK1 subcellular localization determines metabolic phenotype. Dual luciferase reporter assay, chromatin immunoprecipitation, subcellular fractionation, metabolomics, in vitro and in vivo functional assays Gut Medium 31611300
2023 A mitochondria-encoded circular RNA (mcPGK1) promotes PGK1 mitochondrial import via TOM40 interactions, reprogramming metabolism from oxidative phosphorylation to glycolysis through the PGK1-PDK1-PDH axis, and sustaining liver tumor-initiating cell self-renewal. Co-immunoprecipitation, subcellular fractionation, loss-of-function, xenograft and sphere-formation assays, metabolic assays Nature communications Medium 36849569
2023 Extracellular PGK1 directly interacts with neural membrane Enolase-2 (but not Enolase-1 or Enolase-3) through domain mapping (PGK1 residues 325-417 with Enolase-2 residues 405-431). This interaction reduces p-P38-T180/p-Limk1-S323/p-Cofilin signaling and promotes neurite outgrowth of motor neurons. Co-immunoprecipitation, immunoelectron microscopy, domain truncation/mutagenesis, neurite outgrowth assays Communications biology Medium 37582937
2020 PGK1 inhibition by CBR-470-1 leads to methylglyoxal modification of Keap1, causing Keap1-Nrf2 disassociation and activation of the Nrf2 antioxidant cascade, thereby protecting neuronal cells from MPP+-induced cytotoxicity. PGK1 depletion or knockout mimicked these protective effects. Pharmacological inhibition, CRISPR/Cas9 knockout, shRNA knockdown, Nrf2 reporter assays, cell viability assays Aging Medium 32649311
2020 PGK1's forward reaction kinetics were directly measured: Km for 1,3-bisphosphoglyceric acid is 6.86 μM (human PGK1) and for 3-phosphoglycerate (reverse substrate) is 186 μM. The Vmax of the forward reaction is ~5.8-fold higher than the reverse (human). siRNA-mediated PGK1 knockdown in five cancer cell lines and cell-free glycolysis titration revealed that PGK1 perturbation has only marginal effects on glycolytic flux (glucose consumption/lactate production). In vitro enzyme kinetic assays, siRNA knockdown, cell-free glycolysis reconstitution, metabolite measurements The Journal of biological chemistry High 32217690
2020 PGK1 interacts with androgen receptor (AR) in granulosa cells, inhibits AR ubiquitination through an SKP2-dependent mechanism, and increases AR stability, promoting nuclear translocation of AR and regulating expression of key ovulation-related genes. Co-immunoprecipitation, GST pull-down, co-localization, ubiquitination assays, RNA-seq, mouse PCOS model EBioMedicine Medium 33096483
2021 PGK1 couples with Hsp90 via Hsp90's C-terminal domain; this interaction facilitates the binding of GSK3β to Hsp90 in its 'closed' conformation, stabilizing GSK3β expression in an Hsp90 activity-dependent manner and thereby maintaining breast cancer stem cell stemness. Co-immunoprecipitation, mass spectrometry, domain-mapping with Hsp90α mutants, bacterially purified protein binding assays, mammosphere assays Cancer biology & medicine Medium 34403222
2023 KIF15 promotes PGK1 protein stability by recruiting USP10 to PGK1 through KIF15's coil2 domain, thereby facilitating PGK1 deubiquitination, preventing its proteasomal degradation, and enhancing glycolytic capacity in pancreatic cancer cells. Co-immunoprecipitation, mass spectrometry, ubiquitination assay, domain-truncation mutagenesis, xenograft models Cell death & disease Medium 36807568
2008 In developing mouse tooth germ, Pgk1 protein forms an 84-kDa complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as shown by immunoprecipitation-western blotting, with overlapping immunofluorescence expression of both proteins. Immunoprecipitation, western blotting, immunofluorescence Histology and histopathology Low 18228199
2023 PGK1 interacts with ITI-H4 (inter-α-trypsin inhibitor heavy chain 4), increases ITI-H4 expression, and blocks KLKB1-mediated cleavage of ITI-H4. PGK1 also inhibits pro-inflammatory signaling by suppressing the JAK2/STAT3 pathway, modulating the balance between pro- and anti-inflammatory cytokines. Co-immunoprecipitation, MALDI-TOF/MS, cell-based assays Biomedicine & pharmacotherapy Low 36841032
2022 Terazosin activates Pgk1, increasing intracellular ATP levels, which are critical for reducing pathological protein aggregate density. Pgk1 activation also enhances Hsp90 interaction with ULK1 (a master autophagy regulator), promoting autophagy-mediated clearance of condensates, and reducing protein aggregates in models of neurodegenerative disease. Pharmacological activation, primary neuron culture, Drosophila and mouse/rat disease models, co-immunoprecipitation Molecular neurobiology Medium 37249790
2022 A potent ATP-competitive PGK1 inhibitor (DC-PGKI, Kd = 99.08 nM) suppresses both glycolytic activity and the protein kinase function of PGK1, and reveals that PGK1 regulates IL-1β and IL-6 production in LPS-stimulated macrophages. Mechanistically, PGK1 inhibition leads to NRF2 accumulation and nuclear translocation, where NRF2 binds near Il-1β and Il-6 genes to suppress their expression. High-throughput screening, enzymatic inhibition assays, NRF2 reporter assays, chromatin immunoprecipitation, DSS colitis mouse model Acta pharmaceutica Sinica. B Medium 36386479

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 404 26942675
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 274 31911580
2018 Macrophage-Associated PGK1 Phosphorylation Promotes Aerobic Glycolysis and Tumorigenesis. Molecular cell 262 30029001
2016 Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis. Hepatology (Baltimore, Md.) 228 27774669
1990 Measurement by quantitative PCR of changes in HPRT, PGK-1, PGK-2, APRT, MTase, and Zfy gene transcripts during mouse spermatogenesis. Nucleic acids research 226 1690874
1991 The mouse Pgk-1 gene promoter contains an upstream activator sequence. Nucleic acids research 203 1945853
2019 PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1. Molecular cell 175 31492635
2017 MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway. Cancer research 155 28923857
2019 PGK1-mediated cancer progression and drug resistance. American journal of cancer research 127 31815035
2019 Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer. Gut 126 31611300
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
2014 Terazosin activates Pgk1 and Hsp90 to promote stress resistance. Nature chemical biology 119 25383758
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 108 33940159
2017 Protein kinase activity of the glycolytic enzyme PGK1 regulates autophagy to promote tumorigenesis. Autophagy 93 28486006
1990 Polymorphisms in the coding and noncoding regions of murine Pgk-1 alleles. Biochemical genetics 92 1975492
2015 Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1. PLoS biology 83 26356530
1992 The rate-limiting step in yeast PGK1 mRNA degradation is an endonucleolytic cleavage in the 3'-terminal part of the coding region. Molecular and cellular biology 83 1320194
2002 Overexpression of human phosphoglycerate kinase 1 (PGK1) induces a multidrug resistance phenotype. Anticancer research 79 12174867
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
2020 Phosphoglycerate kinase 1 (PGK1) in cancer: A promising target for diagnosis and therapy. Life sciences 71 32479953
1999 The cis acting sequences responsible for the differential decay of the unstable MFA2 and stable PGK1 transcripts in yeast include the context of the translational start codon. RNA (New York, N.Y.) 70 10094310
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 69 30537744
2001 The metabolic burden of the PGK1 and ADH2 promoter systems for heterologous xylanase production by Saccharomyces cerevisiae in defined medium. Biotechnology and bioengineering 68 11257606
2022 LncRNA NEAT1 facilitates glioma progression via stabilizing PGK1. Journal of translational medicine 66 35123484
1990 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5' CpG island. Proceedings of the National Academy of Sciences of the United States of America 66 1693431
2019 Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1. Cell death & disease 61 31827081
2018 Nuclear PGK1 Alleviates ADP-Dependent Inhibition of CDC7 to Promote DNA Replication. Molecular cell 60 30392930
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
2023 mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs. Nature communications 55 36849569
2017 Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis. Cancer chemotherapy and pharmacology 48 28391351
2020 Novel PGK1 determines SKP2-dependent AR stability and reprograms granular cell glucose metabolism facilitating ovulation dysfunction. EBioMedicine 47 33096483
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
2024 PRMT1-mediated PGK1 arginine methylation promotes colorectal cancer glycolysis and tumorigenesis. Cell death & disease 45 38402202
2024 Hypoxia-induced downregulation of PGK1 crotonylation promotes tumorigenesis by coordinating glycolysis and the TCA cycle. Nature communications 45 39134530
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.] 42 27342824
2024 HIF1α/ATF3 partake in PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma. Neuro-oncology 41 38441561
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
2017 Co-opting ATP-generating glycolytic enzyme PGK1 phosphoglycerate kinase facilitates the assembly of viral replicase complexes. PLoS pathogens 36 29059239
1993 A factor stimulating transcription of the testis-specific Pgk-2 gene recognizes a sequence similar to the binding site for a transcription inhibitor of the somatic-type Pgk-1 gene. Nucleic acids research 36 8441629
2023 The Role of PGK1 in Promoting Ischemia/Reperfusion Injury-Induced Microglial M1 Polarization and Inflammation by Regulating Glycolysis. Neuromolecular medicine 35 36749430
2022 Therapeutic inhibition of PPARα-HIF1α-PGK1 signaling targets leukemia stem and progenitor cells in acute myeloid leukemia. Cancer letters 35 36396101
2020 GBP1 promotes erlotinib resistance via PGK1‑activated EMT signaling in non‑small cell lung cancer. International journal of oncology 35 32582960
2019 miR-548c-5p inhibits colorectal cancer cell proliferation by targeting PGK1. Journal of cellular physiology 35 30932211
2018 Dysfunction of pseudogene PGK1P2 is involved in preeclampsia by acting as a competing endogenous RNA of PGK1. Pregnancy hypertension 35 30177069
2022 A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1β and IL-6. Acta pharmaceutica Sinica. B 33 36386479
2020 MiRNA-215-5p alleviates the metastasis of prostate cancer by targeting PGK1. European review for medical and pharmacological sciences 32 32017004
2004 Two proliferation-related proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+ colon cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 31 15355913
2022 Evodiamine prevents traumatic brain injury through inhibiting oxidative stress via PGK1/NRF2 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 36076551
1992 A potentially critical Hpa II site of the X chromosome-linked PGK1 gene is unmethylated prior to the onset of meiosis of human oogenic cells. Proceedings of the National Academy of Sciences of the United States of America 30 1371357
2019 Parkinsonism in PGK1 deficiency implicates the glycolytic pathway in nigrostriatal dysfunction. Parkinsonism & related disorders 29 30975619
2022 PGK1 represses autophagy-mediated cell death to promote the proliferation of liver cancer cells by phosphorylating PRAS40. Cell death & disease 28 35058442
2022 A novel inhibitor of PGK1 suppresses the aerobic glycolysis and proliferation of hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 36516697
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
1993 Methylation analysis by genomic sequencing of 5' region of mouse Pgk-1 gene and a cautionary note concerning the method. Somatic cell and molecular genetics 26 7510422
1991 Timing of paternal Pgk-1 expression in embryos of transgenic mice. Development (Cambridge, England) 25 1879353
2024 Glycolytic enzyme PGK1 promotes M1 macrophage polarization and induces pyroptosis of acute lung injury via regulation of NLRP3. Respiratory research 24 39080660
2023 KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer. Cell death & disease 24 36807568
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
2021 PTCSC3-mediated glycolysis suppresses thyroid cancer progression via interfering with PGK1 degradation. Journal of cellular and molecular medicine 23 34337858
2021 Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders. International journal of molecular sciences 22 35008842
2023 Activation of Pgk1 Results in Reduced Protein Aggregation in Diverse Neurodegenerative Conditions. Molecular neurobiology 21 37249790
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
2022 N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability. Journal of cancer research and clinical oncology 19 36171455
2013 PGK1 as predictor of CXCR4 expression, bone marrow metastases and survival in neuroblastoma. PloS one 18 24376734
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
2006 Intronic mutation in the PGK1 gene may cause recurrent myoglobinuria by aberrant splicing. Neurology 17 16567715
2022 Blockade of PGK1 and ALDOA enhances bilirubin control of Th17 cells in Crohn's disease. Communications biology 16 36131123
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
2007 Altered expression of PGK1 in a family with phosphoglycerate kinase deficiency. Muscle & nerve 15 17661373
2024 Albiflorin alleviates neuroinflammation of rats after MCAO via PGK1/Nrf2/HO-1 signaling pathway. International immunopharmacology 14 38870884
2024 TRIM50 inhibits glycolysis and the malignant progression of gastric cancer by ubiquitinating PGK1. International journal of biological sciences 14 38993561
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
2021 HPV16 E6/E7 stabilize PGK1 protein by reducing its poly-ubiquitination in cervical cancer. Cell biology international 14 34882921
2008 Glycolytic enzyme Pgk1 is strongly expressed in the developing tooth germ of the mouse lower first molar. Histology and histopathology 14 18228199
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
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 CircGLIS3 promotes gastric cancer progression by regulating the miR-1343-3p/PGK1 pathway and inhibiting vimentin phosphorylation. Journal of translational medicine 12 38459513
2023 Targeting the Glycolytic Enzyme PGK1 to Inhibit the Warburg Effect: A New Strategy for Keloid Therapy. Plastic and reconstructive surgery 12 36728674
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 12 38098044
2022 Circ_0076305 facilitates prostate cancer development via sponging miR-411-5p and regulating PGK1. Andrologia 12 35238066
2022 The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents. Frontiers in pharmacology 11 35387336
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 11 35715622
2018 Phylogenetic relationships in the genus Avena based on the nuclear Pgk1 gene. PloS one 11 30408035
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 10 37946295
2023 Intervention of Tanshinone IIA on the PGK1-PDHK1 Pathway to Reprogram Macrophage Phenotype After Myocardial Infarction. Cardiovascular drugs and therapy 10 37991600
2022 Cerebroventricular Injection of Pgk1 Attenuates MPTP-Induced Neuronal Toxicity in Dopaminergic Cells in Zebrafish Brain in a Glycolysis-Independent Manner. International journal of molecular sciences 10 35456967