Affinage

PDK2

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial · UniProt Q15119

Length
407 aa
Mass
46.2 kDa
Annotated
2026-04-29
47 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDK2 is a mitochondrial serine/threonine kinase that phosphorylates and inactivates the E1α subunit of the pyruvate dehydrogenase complex (PDC), acting as a central gatekeeper of mitochondrial oxidative glucose metabolism in the fed state, with PDK4 complementing this role during fasting (PMID:22360721, PMID:14641018). PDK2 is transcriptionally upregulated by c-Myc (stabilized via OGT/O-GlcNAcylation), glucocorticoid receptors, and loss of p53, linking oncogenic and stress signaling to suppression of pyruvate oxidation and promotion of aerobic glycolysis (PMID:22123926, PMID:38778217, PMID:37188779). Beyond its canonical PDC substrate, PDK2 phosphorylates the mitochondrial rhomboid protease PARL to regulate PINK1/PARKIN-dependent mitophagy, and phosphorylates the transcription factor FOXK2 at Thr13/Ser30 to sustain a positive transcriptional feedback loop that reinforces glycolysis (PMID:28178523, PMID:38734828). PDK2 deficiency in mice suppresses osteoclast differentiation via reduced CREB/c-FOS/NFATc1 signaling and prevents ovariectomy-induced bone loss (PMID:33125772).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    The identity of the kinase responsible for Akt Ser473 ('PDK2 site') phosphorylation was unclear; reconstitution showed that PDK1 itself acquires Ser473-kinase activity when bound by a hydrophobic-motif peptide (PIF), suggesting PDK1 and PDK2 could be the same enzyme regulated by interacting proteins.

    Evidence In vitro kinase assays with synthetic PIF peptide, PKBα substrate, and PDK1 immunoprecipitates from brain extract

    PMID:10226025

    Open questions at the time
    • Physiological identity of PDK2 for Akt Ser473 in vivo unresolved
    • Role of mTORC2 not yet discovered at this stage
  2. 2000 High

    An alternative mechanism for Ser473 phosphorylation was established: catalytically competent Akt autophosphorylates Ser473 after PDK1-mediated activation-loop phosphorylation, showing that the PDK2 activity for Akt can be intramolecular.

    Evidence In vivo and in vitro phosphorylation assays with kinase-dead and activation-loop mutant Akt constructs

    PMID:10722653

    Open questions at the time
    • Whether autophosphorylation is the dominant mechanism in physiological contexts remains unclear
    • Contribution of distinct upstream kinases not resolved
  3. 2002 Medium

    PKCζ was identified as an adaptor that delivers a staurosporine-insensitive PDK2 activity to PKBγ via its PH domain, establishing that the PDK2 function for AGC kinases can involve multi-protein complexes rather than a single dedicated enzyme.

    Evidence Yeast two-hybrid, endogenous Co-IP in COS-1 and 3T3-L1 cells, in vitro kinase assay on PKCζ immunoprecipitates

    PMID:12162751

    Open questions at the time
    • Identity of the catalytic kinase within the PKCζ complex not determined
    • Not independently replicated by other labs
  4. 2003 High

    The first potent and selective pharmacological inhibitor of mitochondrial PDK2 (AZD7545) was shown to activate PDH in vivo, establishing that PDK2's phosphorylation of PDH E1 is the rate-limiting step controlling pyruvate oxidation in liver and muscle.

    Evidence In vitro PDH kinase assay (EC50 ~5.2 nM); in vivo PDH activity in rat liver/muscle; glucose profiling in obese Zucker rats

    PMID:14641018

    Open questions at the time
    • Isoform selectivity of AZD7545 vs PDK1/3/4 not fully defined
    • Long-term metabolic consequences not evaluated
  5. 2008 High

    The allosteric regulation of PDK2 was dissected: PDK2 binds the E2 lipoyl domain via a K⁺-dependent site, and phosphate enables metabolite-responsive regulation; the inhibitor Nov3r blocks E2 binding and allosterically disrupts ADP/pyruvate sensing, revealing how PDK2 activity is tuned by mitochondrial metabolite status.

    Evidence Biochemical binding assays, analytical ultracentrifugation for dimer/tetramer equilibrium, competitive inhibition experiments

    PMID:18220415

    Open questions at the time
    • In vivo significance of dimer-to-tetramer transition unknown
    • Structural basis of K⁺-dependent binding not resolved at atomic level at this stage
  6. 2011 Medium

    PDK2 was linked to the Warburg effect in cancer: wild-type p53 transcriptionally represses PDK2, and loss of p53 derepresses PDK2, increasing PDH phosphorylation and lactate production—establishing a direct p53-PDK2-PDC axis governing tumor glycolysis.

    Evidence p53 knockdown/overexpression in cancer cells; PDK2 mRNA/protein, phospho-PDC, and lactate measurements; ChIP/promoter assays

    PMID:22123926

    Open questions at the time
    • Relative contribution of PDK2 vs other PDK isoforms downstream of p53 not dissected
    • In vivo tumor models not reported
  7. 2012 High

    Genetic knockout established that PDK2 is the dominant PDH kinase in the fed state: PDK2/PDK4 double-knockout mice show markedly elevated PDC activity and improved glucose tolerance but develop fatal hypoglycemia during fasting, defining the non-redundant metabolic roles of the two isoforms.

    Evidence Single- and double-knockout mice; tissue PDC activity; blood metabolites; stable isotope flux analysis

    PMID:22360721

    Open questions at the time
    • Whether PDK1/PDK3 partially compensate in specific tissues unclear
    • Tissue-specific conditional knockouts not performed
  8. 2017 High

    A non-canonical substrate of PDK2 was identified: PDK2 phosphorylates PARL, regulating its autocatalytic β-cleavage and thereby negatively controlling PINK1/PARKIN mitophagy, revealing that PDK2 integrates metabolic status with mitochondrial quality control.

    Evidence In vitro kinase assay of PDK2 on PARL; PARL β-cleavage assays; mitophagy reporters; Co-IP of PDK2 and PARL

    PMID:28178523

    Open questions at the time
    • Phosphosite(s) on PARL not mapped
    • Whether other PDK isoforms also phosphorylate PARL not tested
  9. 2020 High

    Structural studies revealed that PDK2 exists as an asymmetric dimer with allosteric crosstalk between the lipoyl-binding and ATP-binding pockets, providing a structural framework for inhibitor design targeting either site.

    Evidence X-ray co-crystal structures of PDK2 with lipoyl-site and ATP-site inhibitors; ITC binding measurements

    PMID:32444142

    Open questions at the time
    • No full-length PDK2-E2 complex structure
    • Dynamics of asymmetry in solution not characterized
  10. 2020 High

    PDK2 was shown to regulate osteoclast differentiation: PDK2 deficiency suppresses RANKL-driven CREB/c-FOS/NFATc1 signaling and prevents ovariectomy-induced bone loss, establishing a role for PDK2 beyond canonical metabolic regulation.

    Evidence Pdk2−/− mice; ovariectomy model; AZD7545 pharmacological rescue; osteoclast differentiation assays from bone marrow monocytes

    PMID:33125772

    Open questions at the time
    • Whether PDK2 directly phosphorylates CREB or acts via PDH-dependent metabolic shift not resolved
    • Cell-autonomous vs systemic contributions not fully dissected
  11. 2023 High

    Glucocorticoid receptor was identified as a direct transcriptional activator of PDK2: GR binds the PDK2 promoter, and neuron-specific PDK2 silencing restores PDH activity and TCA cycle flux, producing antidepressant effects—linking stress-hormone signaling to neuronal metabolic reprogramming via PDK2.

    Evidence GR ChIP on PDK2 promoter; PDK2 shRNA in neurons and in vivo; U-13C glucose isotope tracing; behavioral assays in CSDS mice

    PMID:37188779

    Open questions at the time
    • Whether PDK2 is sufficient to drive depressive-like behavior not shown
    • GR-PDK2 axis in other brain regions not explored
  12. 2024 High

    A second non-canonical substrate was identified: PDK2 phosphorylates FOXK2 at Thr13/Ser30, enhancing its transcriptional activity, while FOXK2 reciprocally upregulates PDK2 expression, establishing a positive feedback loop that sustains glycolysis in cancer cells.

    Evidence Co-IP; in vitro kinase assay with phosphosite identification; phosphomimetic/null mutagenesis; luciferase reporter; glycolysis assays

    PMID:38734828

    Open questions at the time
    • Whether this feedback loop operates outside ovarian cancer unknown
    • Structural basis of PDK2-FOXK2 FHA domain interaction not resolved
  13. 2024 High

    OGT/O-GlcNAc-stabilized c-Myc was shown to transcriptionally upregulate PDK2, connecting nutrient-sensing glycosylation to PDK2-mediated PDH inactivation, ROS suppression, and tumor growth.

    Evidence OGT knockdown; c-Myc S415A mutagenesis; ChIP for c-Myc on PDK2 promoter; PDH activity assays; xenograft models

    PMID:38778217

    Open questions at the time
    • Whether c-Myc-PDK2 axis is active in non-transformed cells not examined
    • Relative contribution of PDK2 among c-Myc glycolytic targets not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the full spectrum of PDK2 non-canonical substrates; the structural basis of the PDK2-E2 holocomplex; whether the PDK2-PARL and PDK2-FOXK2 axes operate in normal physiology; and the tissue-specific transcriptional regulation that determines PDK2 vs other PDK isoform dominance.
  • No phosphoproteomics-based global substrate identification for PDK2
  • No cryo-EM or crystal structure of PDK2 in native E2 complex
  • Tissue-resolved isoform-specific contribution remains unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 3
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-1430728 Metabolism 8 R-HSA-162582 Signal Transduction 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 2
Partners
DLATFOXK2MYCNR3C1PARLPDHA1
Complex memberships
Pyruvate dehydrogenase complex (PDC, as regulatory kinase)

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PDK1 acquires PDK2 activity (phosphorylation of Ser473 of PKBα) in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 (the PIF peptide), which contains a consensus PDK2 motif; this interaction also converts PDK1 from a PtdIns(3,4,5)P3-insensitive to a PtdIns(3,4,5)P3-sensitive form, suggesting PDK1 and PDK2 may be the same enzyme whose substrate specificity is regulated by interacting proteins In vitro kinase assays with synthetic PIF peptide and PKBα substrate; PDK1 immunoprecipitation from brain extract; site-directed mutagenesis of PDK2 consensus motif Current biology : CB High 10226025
1999 The hydrophobic motif site of SGK (Ser422, equivalent to the PDK2 site) is phosphorylated in a PtdIns(3,4,5)P3-dependent manner downstream of IGF-1 or H2O2 signaling; mutation of Ser422 abolishes PDK1-mediated activation of SGK in vitro, while Ser422Asp mimics PDK2 phosphorylation and enables PDK1-independent activation, consistent with a model where a PDK2 activity phosphorylates Ser422 first In vitro kinase assay with PDK1 and SGK; site-directed mutagenesis (Ser422Ala, Ser422Asp); transfection and stimulation in 293 cells; PI3K inhibitor treatment The Biochemical journal High 10191262
2000 Phosphorylation of the hydrophobic motif site of Akt (Ser-473) requires catalytically competent Akt; kinase-inactive Akt fails to incorporate phosphate at Ser-473 in vivo, and PDK-1-activated wild-type Akt autophosphorylates Ser-473 in vitro, establishing Akt autophosphorylation as a mechanism for the PDK-2 site In vivo phosphorylation with kinase-inactive and activation-loop mutant (T308A) Akt constructs; in vitro autophosphorylation assay after PDK-1 activation; thermal inactivation controls The Journal of biological chemistry High 10722653
2002 An independent PDK2 activity that phosphorylates Ser472 of PKBγ physically associates with PKCζ; PKCζ functions as an adaptor that delivers this staurosporine-insensitive PDK2 to PKBγ via the PH domain of PKBγ, enabling phosphorylation of the C-terminal hydrophobic site Yeast two-hybrid screen; endogenous Co-immunoprecipitation in cos-1 cells and 3T3-L1 adipocytes; in vitro kinase assay on PKCζ immunoprecipitates; antisense knockdown; PDK1 inhibitor and staurosporine treatment Biochemistry Medium 12162751
2003 AZD7545, a small-molecule inhibitor of PDHK2 (pyruvate dehydrogenase kinase 2), activates PDH in vivo by preventing phosphorylation of its E1 subunit; a single dose increases active (dephosphorylated) PDH in liver and skeletal muscle of rats, and twice-daily dosing for 7 days improves postprandial glucose control in obese Zucker rats In vitro PDH kinase assay (EC50 ~5.2 nM); rat hepatocyte pyruvate oxidation assay; in vivo PDH activity measurement in liver and muscle; glucose profiling in obese Zucker rats Biochemical Society transactions High 14641018
2004 In yeast, phosphorylation at the PDK1 activation-loop site of AGC kinases Ypk1, Pkc1, and Sch9 is indispensable for their essential in vivo functions, whereas phosphorylation at the PDK2 hydrophobic motif site plays a non-essential modulatory role Genetic epistasis using phosphorylation-site mutants; biochemical assays of kinase activity in yeast Microbiology (Reading, England) Medium 15470109
2006 ORP9S (an N-terminal truncated oxysterol-binding protein-related protein) contains a PDK-2 consensus phosphorylation site at S287 and is directly phosphorylated at this site by PKC-β (confirmed by Co-IP and in vitro kinase assay); ORP9L depletion increases Akt S473 phosphorylation ~3-fold without affecting T308, identifying ORP9 as a PDK-2 substrate and negative regulator of Akt phosphorylation at the PDK-2 site Site-directed mutagenesis of S287; Co-immunoprecipitation of PKC-β and ORP9S; in vitro phosphorylation; RNAi knockdown in HEK293 cells; mTOR inhibitor treatment Cellular signalling Medium 16962287
2008 PDHK2 binds to the L2 lipoyl domain (of E2) via a distinct K+-dependent binding site separate from its active site; phosphate (Pi) is required for ADP/ATP/pyruvate to interfere with PDHK2–GST-L2 binding and promotes PDHK2 dimer-to-tetramer conversion; the lipoyl-group binding site inhibitor Nov3r (IC50 ~7.8 nM for E2-activated PDHK2) prevents PDHK2 binding to E2/GST-L2 and allosterically interferes with ADP and pyruvate binding in a Pi-dependent manner Biochemical binding assays; analytical ultracentrifugation (dimer/tetramer); enzyme activity assays with ions and inhibitors; competitive binding experiments Biochemistry High 18220415
2011 Wild-type p53 transcriptionally represses PDK2 expression, reducing phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC) and thereby decreasing lactate production and limiting the Warburg effect in cancer cells p53 knockdown/overexpression in cancer cell lines; measurement of PDK2 mRNA and protein, phospho-PDC levels, lactate production; ChIP/promoter assays Cancer research Medium 22123926
2012 PDHK2 and PDHK4 together regulate pyruvate dehydrogenase complex (PDC) activity in complementary metabolic states: PDHK2 is dominant in the fed state and PDHK4 in the fasted state; double knockout mice show markedly elevated PDC activity, improved glucose tolerance, increased insulin sensitivity, but develop fatal hypoglycemia, ketoacidosis, and hypothermia during prolonged fasting due to impaired gluconeogenesis Single- and double-knockout mouse models; PDC activity assays in tissue; blood glucose, insulin, and ketone measurements; stable isotope flux analysis The Biochemical journal High 22360721
2015 PDK2 inhibition in cancer cells (via PDK2 knockdown or DCA) rapidly induces mitochondrial perturbations and shifts Bnip3 pre-mRNA splicing from the pro-survival Bnip3Δex3 isoform to the pro-death full-length isoform, linking the glycolytic phenotype to hypoxia resistance through a PDK2-dependent alternative splicing mechanism PDK2 knockdown (siRNA) in Panc-1 cells; DCA treatment; RT-PCR for Bnip3 splice isoforms; mitochondrial membrane potential assay; cell death assays The Journal of cell biology Medium 26416963
2017 PDK2 phosphorylates the mitochondrial rhomboid protease PARL, thereby regulating PARL's N-terminal autocatalytic β-cleavage and consequently negatively regulating PINK1/PARKIN-mediated mitophagy; PDK2-mediated PARL phosphorylation thus integrates mitochondrial metabolic status with mitochondrial quality control In vitro kinase assay (PDK2 phosphorylating PARL); PARL β-cleavage assay under mitochondrial stress; mitophagy reporter assays; PDK2 knockdown/overexpression; Co-IP of PDK2 and PARL Cell reports High 28178523
2020 PDK2 overexpression in TAO orbital fibroblasts enhances glycolysis (increased lactate, decreased oxygen consumption) and promotes cell proliferation via Akt signaling; PDK2 knockdown reduces lactate production, increases oxygen consumption, decreases proliferation, and lowers cytoplasmic Akt levels, while Akt inhibition phenocopies PDK2 knockdown PDK2 knockdown (siRNA); lactate and oxygen consumption assays; EdU/BrdU proliferation assays; capillary Western immunoassay of Akt and pAkt308; DCA treatment Journal of molecular endocrinology Medium 33086191
2020 PDK2 deficiency in mice suppresses osteoclast differentiation by reducing phosphorylation of CREB and c-FOS and consequently lowering NFATc1 transcription downstream of RANKL signaling; PDK2 knockout prevents ovariectomy-induced bone loss and the PDK2-specific inhibitor AZD7545 recapitulates this effect Pdk2−/− mouse model; ovariectomy model; AZD7545 pharmacological inhibition; CREB/c-FOS/NFATc1 protein assays; osteoclast differentiation assays from bone marrow-derived monocytes Journal of bone and mineral research High 33125772
2020 Crystal structures of PDK2 complexed with (1) a lipoyl-binding site inhibitor (compound 8c) reveal its binding location and a remote conformational change in the ATP-binding pocket, and (2) ATP-site inhibitors (GM10030, GM67520, diarylisoxazole derivatives binding sub-100 nM) show an unprecedented asymmetric conformation of the human PDK2 dimer, particularly in the ATP-lids and C-terminal tails X-ray crystallography of PDK2 co-crystal structures; isothermal titration calorimetry for binding affinity Biochemical and biophysical research communications High 32444142
2023 PDK2 phosphorylates and regulates PARL within the SIRT1/PDK2/PARL axis; oroxylin A inhibits this axis, preventing mitochondrial fusion and breaking metabolic plasticity in hepatocellular carcinoma cells, sensitizing them to glucose restriction SIRT1/PDK2/PARL pathway analysis; mitochondrial fusion assays; spare respiratory capacity (SRC) measurement; cell viability under glucose restriction; combination treatment experiments Biomedicine & pharmacotherapy Medium 37633053
2023 Glucocorticoid receptors (GR) directly bind the PDK2 promoter to stimulate PDK2 expression; elevated PDK2 phosphorylates and inactivates PDH, suppressing TCA cycle flux and oxidative phosphorylation in neurons; neuron-specific silencing of PDK2 restores PDH activity, normalizes 13C-glucose flux into the TCA cycle, and exerts antidepressant effects in chronic social defeat stress mice GR ChIP on PDK2 promoter; PDK2 siRNA/shRNA in neurons and in vivo; isotope tracing (U-13C glucose); PDH activity assay; mitochondrial OXPHOS measurement; behavioral assays in CSDS mice Molecular psychiatry High 37188779
2024 PDK2 directly binds the forkhead-associated (FHA) domain of the transcription factor FOXK2 and phosphorylates it at Thr13 and Ser30, enhancing FOXK2 transcriptional activity; FOXK2 in turn transcriptionally upregulates PDK2 expression, forming a positive feedback loop that sustains glycolysis in ovarian cancer cells Co-IP of PDK2 and FOXK2; in vitro kinase assay with phosphosite identification; phosphomimetic/phospho-null mutagenesis; luciferase reporter assay for PDK2 promoter activity; glycolysis assays; cell proliferation and migration assays Oncogene High 38734828
2024 OGT-catalyzed O-GlcNAc modification of c-Myc at Ser415 stabilizes c-Myc protein, which transcriptionally upregulates PDK2; elevated PDK2 phosphorylates pyruvate dehydrogenase (PDH) E1 subunit to inhibit the PDH complex, reducing mitochondrial pyruvate metabolism and suppressing ROS while promoting tumor growth OGT knockdown; c-Myc mutagenesis (S415A); ChIP for c-Myc binding to PDK2 promoter; PDK2 overexpression/knockdown; PDH phosphorylation and activity assays; TCA flux measurement; xenograft tumor growth Cell death and differentiation High 38778217
2024 Cordycepin targets PDK2 in microglial mitochondria (confirmed by mitochondrial isolation and HPLC-MS/MS), and PDK2 inhibition enhances OCR levels in PDH-mediated OXPHOS, promoting microglial M2 polarization and neuronal survival in an Alzheimer's disease model Mitochondrial isolation followed by HPLC-MS/MS target identification; PDK2 inhibitor experiments; OCR/ECAR measurement; microglial polarization markers; APP/PS1 mouse model Advanced science Medium 38889331

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. The Biochemical journal 496 10191262
2000 Akt/protein kinase B is regulated by autophosphorylation at the hypothetical PDK-2 site. The Journal of biological chemistry 419 10722653
1999 PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2. Current biology : CB 384 10226025
2011 p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2. Cancer research 206 22123926
2005 PDK2: the missing piece in the receptor tyrosine kinase signaling pathway puzzle. American journal of physiology. Endocrinology and metabolism 115 16014356
2004 Differential roles of PDK1- and PDK2-phosphorylation sites in the yeast AGC kinases Ypk1, Pkc1 and Sch9. Microbiology (Reading, England) 98 15470109
2001 PDK2: a complex tail in one Akt. Science's STKE : signal transduction knowledge environment 96 11752635
2019 Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway. Oncogene 86 31597953
2015 Activation of mitochondrial oxidation by PDK2 inhibition reverses cisplatin resistance in head and neck cancer. Cancer letters 75 26607904
2021 DCA Protects against Oxidation Injury Attributed to Cerebral Ischemia-Reperfusion by Regulating Glycolysis through PDK2-PDH-Nrf2 Axis. Oxidative medicine and cellular longevity 73 34712383
2017 The Mitochondrial Rhomboid Protease PARL Is Regulated by PDK2 to Integrate Mitochondrial Quality Control and Metabolism. Cell reports 62 28178523
2003 AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats. Biochemical Society transactions 62 14641018
2024 Cordycepin Modulates Microglial M2 Polarization Coupled with Mitochondrial Metabolic Reprogramming by Targeting HKII and PDK2. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 45 38889331
2006 Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and regulates Akt phosphorylation. Cellular signalling 39 16962287
2012 Fasting induces ketoacidosis and hypothermia in PDHK2/PDHK4-double-knockout mice. The Biochemical journal 38 22360721
2023 Targeting PDK2 rescues stress-induced impaired brain energy metabolism. Molecular psychiatry 37 37188779
2024 The OGT-c-Myc-PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth. Cell death and differentiation 36 38778217
2002 Characterization of PDK2 activity against protein kinase B gamma. Biochemistry 35 12162751
2022 Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells. Journal of microbiology (Seoul, Korea) 31 35781627
2015 PDK2-mediated alternative splicing switches Bnip3 from cell death to cell survival. The Journal of cell biology 31 26416963
1997 A translation frameshift mutation induced by a cytosine insertion in the polycystic kidney disease 2 gene (PDK2). Human molecular genetics 27 9175744
2021 PDK2 leads to cisplatin resistance through suppression of mitochondrial function in ovarian clear cell carcinoma. Cancer science 26 34464482
2020 Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR-422a/PDK2 axis. Cancer medicine 26 32022476
2021 The Use of Vitamin K2 in Patients With Parkinson's Disease and Mitochondrial Dysfunction (PD-K2): A Theranostic Pilot Study in a Placebo-Controlled Parallel Group Design. Frontiers in neurology 24 33505346
2020 PDK2 Deficiency Prevents Ovariectomy-Induced Bone Loss in Mice by Regulating the RANKL-NFATc1 Pathway During Osteoclastogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 22 33125772
2017 PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 21 28225870
2024 Baicalin attenuates neuronal damage associated with SDH activation and PDK2-PDH axis dysfunction in early reperfusion. Phytomedicine : international journal of phytotherapy and phytopharmacology 20 38579645
2022 PDK1- and PDK2-mediated metabolic reprogramming contributes to the TGFβ1-promoted stem-like properties in head and neck cancer. Cancer & metabolism 20 36474273
2018 PDK2 induces cisplatin-resistance in lung adenocarcinoma via transcriptional regulation of CNNM3. Journal of drug targeting 19 30457021
2021 Circular RNA hsa_circ_0005397 promotes hepatocellular carcinoma progression by regulating the miR-326/PDK2 axis. The journal of gene medicine 17 33783904
2019 MicroRNA-214 suppresses cell proliferation and migration and cell metabolism by targeting PDK2 and PHF6 in hepatocellular carcinoma. Cell biology international 16 31329335
2022 circPTP4A2-miR-330-5p-PDK2 Signaling Facilitates In Vivo Survival of HuMSCs on SF-SIS Scaffolds and Improves the Repair of Damaged Endometrium. Oxidative medicine and cellular longevity 15 35571241
2019 Membrane-initiated cortisol action modulates early pyruvate dehydrogenase kinase 2 (pdk2) expression in fish skeletal muscle. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 15 30930204
2011 Chronic CSE treatment induces the growth of normal oral keratinocytes via PDK2 upregulation, increased glycolysis and HIF1α stabilization. PloS one 13 21283817
2008 Specific ion influences on self-association of pyruvate dehydrogenase kinase isoform 2 (PDHK2), binding of PDHK2 to the L2 lipoyl domain, and effects of the lipoyl group-binding site inhibitor, Nov3r. Biochemistry 12 18220415
2022 Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity. Animal nutrition (Zhongguo xu mu shou yi xue hui) 9 36016966
2021 Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis. Open life sciences 9 33817300
2020 PDK2-enhanced glycolysis promotes fibroblast proliferation in thyroid-associated ophthalmopathy. Journal of molecular endocrinology 9 33086191
2016 The Novel Small Molecule Inhibitor, OSU-T315, Suppresses Vestibular Schwannoma and Meningioma Growth by Inhibiting PDK2 Function in the AKT Pathway Activation. Austin journal of medical oncology 8 27642646
2024 Phosphorylation of FOXK2 at Thr13 and Ser30 by PDK2 sustains glycolysis through a positive feedback manner in ovarian cancer. Oncogene 6 38734828
2022 Chemokine (C-X-C motif) ligand 1 maintains the immune surveillance function of natural killer cells via the PDK2/mTOR signaling pathway. Cell biology and toxicology 6 35304656
2016 PDK2 and ABCG2 genes polymorphisms are correlated with blood glucose levels and uric acid in Tibetan gout patients. Genetics and molecular research : GMR 6 26909964
2024 Mitochondrial-related genes PDK2, CHDH, and ALDH5A1 served as a diagnostic signature and correlated with immune cell infiltration in ulcerative colitis. Aging 5 38376420
2023 Inhibition of mitochondrial fusion via SIRT1/PDK2/PARL axis breaks mitochondrial metabolic plasticity and sensitizes cancer cells to glucose restriction therapy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 5 37633053
2012 PDHK-2 deficiency is associated with attenuation of lipase-mediated fat consumption for the increased survival of Caenorhabditis elegans dauers. PloS one 4 22848591
2020 Structural basis for the inhibition of PDK2 by novel ATP- and lipoyl-binding site targeting compounds. Biochemical and biophysical research communications 3 32444142
2025 PDK2-enhanced glycolysis aggravates fibrosis via IL11 signaling pathway in Graves' orbitopathy. Frontiers in immunology 1 40018034