PDK2

Summary

Gene Symbol: PDK2
Description: pyruvate dehydrogenase kinase 2
Alias: PDHK2, PDKII, pyruvate dehydrogenase kinase, isozyme 2, PDH kinase 2, [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial, pyruvate dehydrogenase kinase, isoenzyme 2, pyruvate dehydrogenase, lipoamide, kinase isozyme 2, mitochondrial
Species: human
Products:     PDK2

Top Publications

  1. Bao H, Kasten S, Yan X, Hiromasa Y, Roche T. Pyruvate dehydrogenase kinase isoform 2 activity stimulated by speeding up the rate of dissociation of ADP. Biochemistry. 2004;43:13442-51 pubmed
    Pyruvate dehydrogenase kinase 2 (PDK2) activity is stimulated by NADH and NADH plus acetyl-CoA via the reduction and reductive acetylation of the lipoyl groups of the dihydrolipoyl acetyltransferase (E2) component...
  2. Sun W, Zhou S, Chang S, McFate T, Verma A, Califano J. Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma. Clin Cancer Res. 2009;15:476-84 pubmed publisher
    ..levels of HIF1alpha, pyruvate dehydrogenease (PDH), phosphorylated PDH, and pyruvate dehydrogenease kinase 2 (PDK2), together with ROS generation, were compared between the mutant and the wild type...
  3. Tumova S, Kerimi A, Williamson G. Long term treatment with quercetin in contrast to the sulfate and glucuronide conjugates affects HIF1α stability and Nrf2 signaling in endothelial cells and leads to changes in glucose metabolism. Free Radic Biol Med. 2019;: pubmed publisher
    ..Pyruvate dehydrogenase kinase (PDK) isoforms regulate pyruvate dehydrogenase; PDK2 and PDK4 was down-regulated by both effectors, but only DMOG also upregulated PDK1 and PDK3...
  4. Kolekar P, Patil S, Suryavanshi M, Suryawanshi S, Khandare R, Govindwar S, et al. Microcosm study of atrazine bioremediation by indigenous microorganisms and cytotoxicity of biodegraded metabolites. J Hazard Mater. 2019;374:66-73 pubmed publisher
    ..Three isolated bacteria, Rhodococcus sp. BCH2 (RB), Bacillus sp. PDK1 (BP1) and Bacillus sp. PDK2 (BP2) possessing capability to degrade atrazine were used in different combinations (RB + BP1, RB + BP2, ..
  5. Mostoufi A, Baghgoli R, Fereidoonnezhad M. Synthesis, cytotoxicity, apoptosis and molecular docking studies of novel phenylbutyrate derivatives as potential anticancer agents. Comput Biol Chem. 2019;80:128-137 pubmed publisher
    ..The molecular docking studies of the synthesized compounds on pyruvate dehydrogenase kinase 2 (PDK2; PDB ID: 2BU8) and histone deacetylase complex (HDAC; PDB ID: 1C3R), as the main targets of PB were applied to ..
  6. Aedo J, Zuloaga R, Boltaña S, Molina A, Valdés J. Membrane-initiated cortisol action modulates early pyruvate dehydrogenase kinase 2 (pdk2) expression in fish skeletal muscle. Comp Biochem Physiol A Mol Integr Physiol. 2019;233:24-29 pubmed publisher
    ..action over the expression of the critical modulator of energetic metabolism, pyruvate dehydrogenase kinase 2 (pdk2), in fish skeletal muscle...
  7. He Z, Li Z, Zhang X, Yin K, Wang W, Xu Z, et al. MiR-422a regulates cellular metabolism and malignancy by targeting pyruvate dehydrogenase kinase 2 in gastric cancer. Cell Death Dis. 2018;9:505 pubmed publisher
    ..Mechanistic analysis suggested that miR-422a repressed pyruvate dehydrogenase kinase 2 (PDK2) to restore activity of the pyruvate dehydrogenase (PDH), the gatekeeping enzyme that catalyzes the decarboxylation ..
  8. Hao Q, Yadav R, Basse A, Petersen S, Sonne S, Rasmussen S, et al. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2015;308:E380-92 pubmed publisher
    ..Similarly, expression of lactate dehydrogenases was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold...
  9. Cui L, Cheng Z, Liu Y, Dai Y, Pang Y, Jiao Y, et al. Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia. Cancer Gene Ther. 2018;: pubmed publisher
    ..Univariate analysis showed that high expression of PDK2 was associated with shorter EFS (P = 0...

More Information

Publications82

  1. Yang R, Guo C. Discovery of potent pyruvate dehydrogenase kinase inhibitors and evaluation of their anti-lung cancer activity under hypoxia. Medchemcomm. 2018;9:1843-1849 pubmed publisher
    ..26, 0.62, and 0.41 μM against PDK1, respectively, and showed a similar inhibitory effect on PDK2, PDK3, and PDK4...
  2. Klyuyeva A, Tuganova A, Kedishvili N, Popov K. Tissue-specific kinase expression and activity regulate flux through the pyruvate dehydrogenase complex. J Biol Chem. 2019;294:838-851 pubmed publisher
    ..Analysis of protein content of PDK isozymes in major metabolic tissues revealed that PDK1 and PDK2 were ubiquitously expressed, whereas PDK3 and PDK4 displayed a rather limited tissue distribution...
  3. Hao X, Gu H, Chen C, Huang D, Zhao Y, Xie L, et al. Metabolic Imaging Reveals a Unique Preference of Symmetric Cell Division and Homing of Leukemia-Initiating Cells in an Endosteal Niche. Cell Metab. 2019;29:950-965.e6 pubmed publisher
    ..b>PDK2 fine-tunes glycolysis, homing, and symmetric division of LICs...
  4. Wang J, Kumaran S, Zhou J, Nemeria N, Tao H, Kakalis L, et al. Elucidation of the interaction loci of the human pyruvate dehydrogenase complex E2·E3BP core with pyruvate dehydrogenase kinase 1 and kinase 2 by H/D exchange mass spectrometry and nuclear magnetic resonance. Biochemistry. 2015;54:69-82 pubmed publisher
    ..and nuclear magnetic resonance (NMR) studies in the first attempt to define the interaction loci between PDK1 and PDK2 with the intact E2·E3BP core and their C-terminally truncated proteins...
  5. Ferriero R, Iannuzzi C, Manco G, Brunetti Pierri N. Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate. J Inherit Metab Dis. 2015;38:895-904 pubmed publisher
    ..Moreover, docking studies revealed putative binding sites of phenylbutyrate on PDK2 and 3 that are located on different sites compared to dichloroacetate (DCA), a previously known PDK inhibitor...
  6. Takubo K, Nagamatsu G, Kobayashi C, Nakamura Ishizu A, Kobayashi H, Ikeda E, et al. Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell. 2013;12:49-61 pubmed publisher
    ..in glycolysis-defective HSCs restored glycolysis, cell cycle quiescence, and stem cell capacity, while loss of both Pdk2 and Pdk4 attenuated HSC quiescence, glycolysis, and transplantation capacity...
  7. Wu C, Tso S, Chuang J, Gui W, Lou M, Sharma G, et al. Targeting hepatic pyruvate dehydrogenase kinases restores insulin signaling and mitigates ChREBP-mediated lipogenesis in diet-induced obese mice. Mol Metab. 2018;12:12-24 pubmed publisher
    ..inhibitor 2-[(2,4-dihydroxyphenyl) sulfonyl]isoindoline-4,6-diol (PS10) for four weeks, and results compared with PDK2/PDK4 double knockout (DKO) mice on the same high fat diet (HFD)...
  8. Gang B, Dilda P, Hogg P, Blackburn A. Targeting of two aspects of metabolism in breast cancer treatment. Cancer Biol Ther. 2014;15:1533-41 pubmed publisher
    ..oxygen species in both T-47D and MDA-MB-231 cells, however further investigations found it did not always involve PDK2 inhibition or reduction of the mitochondrial membrane potential, which are the accepted mechanisms for DCA ..
  9. Bakre A, Andersen L, Meliopoulos V, Coleman K, Yan X, Brooks P, et al. Identification of Host Kinase Genes Required for Influenza Virus Replication and the Regulatory Role of MicroRNAs. PLoS ONE. 2013;8:e66796 pubmed publisher
    ..From the screen, 17 HPKs (NPR2, MAP3K1, DYRK3, EPHA6, TPK1, PDK2, EXOSC10, NEK8, PLK4, SGK3, NEK3, PANK4, ITPKB, CDC2L5 (CDK13), CALM2, PKN3, and HK2) were validated as essential ..
  10. Byun J, Choi Y, Kang Y, Jang B, Kang K, Jeon Y, et al. Retinoic acid-related orphan receptor alpha reprograms glucose metabolism in glutamine-deficient hepatoma cells. Hepatology. 2015;61:953-64 pubmed publisher
    ..Ad-RORα and SR1078 reduced the expression of pyruvate dehydrogenase kinase 2 (PDK2) and inhibited the phosphorylation of pyruvate dehydrogenase and subsequently shifted pyruvate to complete ..
  11. Yoo H, Kang J, Lee D, Oh S, Lee Y, Lee E, et al. Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury. Biochem Biophys Res Commun. 2015;460:504-10 pubmed publisher
    ..on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway...
  12. Hou X, Zhang L, Han L, Ge J, Ma R, Zhang X, et al. Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturation. J Cell Sci. 2015;128:2319-29 pubmed publisher
    ..Unexpectedly, we discovered that PDK1 and PDK2 promote meiotic maturation, as their knockdown disturbs the assembly of the meiotic apparatus, without ..
  13. Misra S, Ye M, Ostadhossein F, Pan D. Pro-haloacetate Nanoparticles for Efficient Cancer Therapy via Pyruvate Dehydrogenase Kinase Modulation. Sci Rep. 2016;6:28196 pubmed publisher
    ..Through molecular docking studies mono- and dihaloacetates are identified as potent PDK2 binders and matched their efficiency with dichloroacetic acid...
  14. Biensø R, Olesen J, Gliemann L, Schmidt J, Matzen M, Wojtaszewski J, et al. Effects of Exercise Training on Regulation of Skeletal Muscle Glucose Metabolism in Elderly Men. J Gerontol A Biol Sci Med Sci. 2015;70:866-72 pubmed publisher
    ..training increased Hexokinase II, GLUT4, Akt2, glycogen synthase (GS), pyruvate dehydrogenase (PDH)-E1α, PDK2 protein, and glycogen content in skeletal muscle...
  15. Halvarsson C, Eliasson P, Jönsson J. Pyruvate dehydrogenase kinase 1 is essential for transplantable mouse bone marrow hematopoietic stem cell and progenitor function. PLoS ONE. 2017;12:e0171714 pubmed publisher
    ..While the Pdk gene family contains four members (Pdk1-4), it was recently shown that Pdk2 and Pdk4 have an important role in regulating LT-HSCs...
  16. Xu S, Tao J, Yang L, Zhang E, Boriboun C, Zhou J, et al. E2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone Marrow Progenitor Cells. Circ Res. 2018;122:701-711 pubmed publisher
    ..Our results suggest a novel mechanism by which E2F1 mediates the metabolic control of BM PC differentiation, and strategies that inhibit E2F1 or enhance oxidative metabolism in BM PCs may improve the effectiveness of cell therapy. ..
  17. Consitt L, Saxena G, Saneda A, Houmard J. Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training. Am J Physiol Endocrinol Metab. 2016;311:E145-56 pubmed publisher
    ..observed in skeletal muscle phosphorylation of LDH, GSK-3α, or GSK-3β in response to insulin or PDP1, PDP2, PDK2, PDK4, or MPC1 total protein...
  18. Zhang Y, Zhao Z, Ke B, Wan L, Wang H, Ye J. Induction of Posttranslational Modifications of Mitochondrial Proteins by ATP Contributes to Negative Regulation of Mitochondrial Function. PLoS ONE. 2016;11:e0150454 pubmed publisher
    ..was induced by incubation of mitochondrial lysate with ATP in vitro without altering the expression of PDH kinase 2 (PDK2) and 4 (PDK4)...
  19. Mercado Pimentel M, Igarashi S, Dunn A, Behbahani M, Miller C, Read C, et al. The Novel Small Molecule Inhibitor, OSU-T315, Suppresses Vestibular Schwannoma and Meningioma Growth by Inhibiting PDK2 Function in the AKT Pathway Activation. Austin J Med Oncol. 2016;3: pubmed
    Activation of PKB/AKT signaling, which requires PDK1 and PDK2 function, drives Vestibular Schwannoma (VS) and meningioma growth. PDK2 function is defined as a molecule that phosphorylates AKT-Ser473...
  20. Lappe R, Baier J, Boehlein S, Huffman R, Lin Q, Wattebled F, et al. Functions of maize genes encoding pyruvate phosphate dikinase in developing endosperm. Proc Natl Acad Sci U S A. 2018;115:E24-E33 pubmed publisher
    ..Direct targets of the bZIP transcriptional regulator encoded by o2 include pdk1 and pdk2 that specify pyruvate phosphate dikinase (PPDK)...
  21. Huang S, Feng C, Chen L, Huang Z, Zhou X, Li B, et al. Identification of Potential Key Long Non-Coding RNAs and Target Genes Associated with Pneumonia Using Long Non-Coding RNA Sequencing (lncRNA-Seq): A Preliminary Study. Med Sci Monit. 2016;22:3394-3408 pubmed
    ..2, such as QRFP and EPS8. Both upregulated RP11-456D7.1 and RP11-96C23.9 regulated several genes, such as PDK2. RP11-456D7.1 also positively regulated CCL21...
  22. Jha M, Song G, Lee M, Jeoung N, Go Y, Harris R, et al. Metabolic Connection of Inflammatory Pain: Pivotal Role of a Pyruvate Dehydrogenase Kinase-Pyruvate Dehydrogenase-Lactic Acid Axis. J Neurosci. 2015;35:14353-69 pubmed publisher
    ..Deficiency of Pdk2 and/or Pdk4 in mice attenuated complete Freund's adjuvant (CFA)-induced pain hypersensitivities...
  23. Naia L, Cunha Oliveira T, Rodrigues J, Rosenstock T, Oliveira A, Ribeiro M, et al. Histone Deacetylase Inhibitors Protect Against Pyruvate Dehydrogenase Dysfunction in Huntington's Disease. J Neurosci. 2017;37:2776-2794 pubmed publisher
    ..factor-1 (HIF-1?) stabilization and decreased the transcription of the two most abundant PDK isoforms, PDK2 and PDK3, culminating in increased PDH activation in mutant cells...
  24. Wang H, Shan X, Qiao Y. PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway. Braz J Med Biol Res. 2017;50:e5988 pubmed publisher
    This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs)...
  25. Lie S, Morrison J, Williams Wyss O, Suter C, Humphreys D, Ozanne S, et al. Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses. Am J Physiol Endocrinol Metab. 2016;310:E148-59 pubmed publisher
    ..05), PDK2 (P < 0.01), and PDK4 (P < 0.01) mRNA expression in singleton and twin fetuses at 135-138 days gestation...
  26. Ling Z, Shu N, Xu P, Wang F, Zhong Z, Sun B, et al. Involvement of pregnane X receptor in the impaired glucose utilization induced by atorvastatin in hepatocytes. Biochem Pharmacol. 2016;100:98-111 pubmed publisher
    ..Rifampicin/PCN served as PXR activator control. Glucose utilization, glucose uptake, protein levels of GLUT2, GCK, PDK2, PEPCK1 and G6Pase in HepG2 cells were measured...
  27. Rahman M, Jha M, Kim J, Nam Y, Lee M, Go Y, et al. Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy. J Biol Chem. 2016;291:6011-25 pubmed publisher
    ..In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to ..
  28. Knudsen J, Joensen E, Bertholdt L, Jessen H, van Hauen L, Hidalgo J, et al. Skeletal muscle IL-6 and regulation of liver metabolism during high-fat diet and exercise training. Physiol Rep. 2016;4: pubmed publisher
    ..Hepatic pyruvate dehydrogenase kinase (PDK) 4 and PDK2 protein content was in Floxed mice lower in HFD ExTr than Chow...
  29. Yoon S, Kim J, Seo A, Park S, Kim H, Park J, et al. Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer. Oncology. 2015;89:351-9 pubmed publisher
    ..Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by ..
  30. Go Y, Jeong J, Jeoung N, Jeon J, Park B, Kang H, et al. Inhibition of Pyruvate Dehydrogenase Kinase 2 Protects Against Hepatic Steatosis Through Modulation of Tricarboxylic Acid Cycle Anaplerosis and Ketogenesis. Diabetes. 2016;65:2876-87 pubmed publisher
    ..This study examined whether hepatic PDC activation by inhibition of pyruvate dehydrogenase kinase 2 (PDK2) ameliorates these metabolic abnormalities...
  31. Roh J, Park J, Kim E, Jang H, Kwon M. Activation of mitochondrial oxidation by PDK2 inhibition reverses cisplatin resistance in head and neck cancer. Cancer Lett. 2016;371:20-9 pubmed publisher
    ..Cisplatin-resistant cells overexpressed pyruvate dehydrogenase kinase 2 (PDK2). DCA induced HNC cell death by decreasing ΔΨm and promoting mitochondrial ROS production...
  32. Gudi R, Bowker Kinley M, Kedishvili N, Zhao Y, Popov K. Diversity of the pyruvate dehydrogenase kinase gene family in humans. J Biol Chem. 1995;270:28989-94 pubmed
    ..from this laboratory indicates that at least two isoenzymic forms of pyruvate dehydrogenase kinase (PDK1 and PDK2) may be involved in the regulation of enzymatic activity of mammalian pyruvate dehydrogenase complex by ..
  33. Sugden M, Holness M. Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab. 2003;284:E855-62 pubmed
  34. Abbot E, McCormack J, Reynet C, Hassall D, Buchan K, Yeaman S. Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells. FEBS J. 2005;272:3004-14 pubmed
    ..Using a cultured human skeletal muscle cell model system, we found that expression of both PDK2 and PDK4 mRNA is upregulated in response to glucose deprivation and fatty acid supplementation, the effects of ..
  35. Sutendra G, Dromparis P, Kinnaird A, Stenson T, Haromy A, Parker J, et al. Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer. Oncogene. 2013;32:1638-50 pubmed publisher
    ..We show that inhibition of PDKII inhibits HIF1? in cancer cells using several techniques, including HIF1? luciferase reporter assays...
  36. Bao H, Kasten S, Yan X, Roche T. Pyruvate dehydrogenase kinase isoform 2 activity limited and further inhibited by slowing down the rate of dissociation of ADP. Biochemistry. 2004;43:13432-41 pubmed
    Pyruvate dehydrogenase kinase 2 (PDK2) activity is enhanced by the dihydrolipoyl acetyltransferase core (E2 60mer) that binds PDK2 and a large number of its pyruvate dehydrogenase (E1) substrate...
  37. Watt M, Heigenhauser G, Leblanc P, Inglis J, Spriet L, Peters S. Rapid upregulation of pyruvate dehydrogenase kinase activity in human skeletal muscle during prolonged exercise. J Appl Physiol (1985). 2004;97:1261-7 pubmed
    ..The increased PDK activity was independent of changes in intra-mitochondrial effectors, and PDK-2 and PDK-4 protein content, suggesting that it was caused by a change in the specific activity of the existing kinases. ..
  38. Knoechel T, Tucker A, Robinson C, Phillips C, Taylor W, Bungay P, et al. Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands. Biochemistry. 2006;45:402-15 pubmed
    ..Several of the PDHK2 structures disclosed have C-terminal cross arms that span a large trough region between the N-terminal regulatory (..
  39. Degenhardt T, Saramaki A, Malinen M, Rieck M, Väisänen S, Huotari A, et al. Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta. J Mol Biol. 2007;372:341-55 pubmed
    ..In human embryonal kidney cells we found the mRNA expression of PDK2, PDK3 and PDK4 to be under direct primary control of PPAR ligands, and in normal mouse kidney tissue Pdk2 and Pdk4 ..
  40. Hiromasa Y, Roche T. Critical role of specific ions for ligand-induced changes regulating pyruvate dehydrogenase kinase isoform 2. Biochemistry. 2008;47:2298-311 pubmed publisher
    In the complete absence of K+ and phosphate (Pi), pyruvate dehydrogenase kinase isoform 2 (PDHK2) was catalytically very active but with an elevated Km for ATP, and this activity is insensitive to effector regulation...
  41. Ren Y, Jin T, Sun X, Geng T, Zhang M, Wang L, et al. PDK2 and ABCG2 genes polymorphisms are correlated with blood glucose levels and uric acid in Tibetan gout patients. Genet Mol Res. 2016;15: pubmed publisher
    Previous studies have shown that the PDK2 and ABCG2 genes play important roles in many aspects of gout development in European populations. However, a detailed genotype-phenotype analysis was not performed...
  42. Peters S, Harris R, Wu P, Pehleman T, Heigenhauser G, Spriet L. Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet. Am J Physiol Endocrinol Metab. 2001;281:E1151-8 pubmed
    ..Intact mitchondria were extracted from fresh muscle and analyzed for PDK activity and Western blotting of PDK2 and PDK4 protein...
  43. Roche T, Baker J, Yan X, Hiromasa Y, Gong X, Peng T, et al. Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms. Prog Nucleic Acid Res Mol Biol. 2001;70:33-75 pubmed
    ..Overexpression of the same PDK isoforms deleteriously hinders glucose consumption in unregulated diabetes. ..
  44. Hurd T, Collins Y, Abakumova I, Chouchani E, Baranowski B, Fearnley I, et al. Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species. J Biol Chem. 2012;287:35153-60 pubmed publisher
    ..Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic ..
  45. Boulatnikov I, Popov K. Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase. Biochim Biophys Acta. 2003;1645:183-92 pubmed
    ..are four genetically and biochemically distinct forms of PDK that are expressed in a tissue-specific manner (PDK1, PDK2, PDK3, and PDK4)...
  46. Wu C, Chao Y, Shiah S, Lin W. Nutrient deprivation induces the Warburg effect through ROS/AMPK-dependent activation of pyruvate dehydrogenase kinase. Biochim Biophys Acta. 2013;1833:1147-56 pubmed publisher
    ..Such an event contributes to protecting cells from apoptosis upon nutrient deprivation. ..
  47. Hiromasa Y, Roche T. Facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferase. J Biol Chem. 2003;278:33681-93 pubmed
    ..Analytical ultracentrifugation (AUC) studies established that the soluble PDK2 isoform is a stable dimer...
  48. Gudiksen A, Bertholdt L, Stankiewicz T, Tybirk J, Plomgaard P, Bangsbo J, et al. Effects of training status on PDH regulation in human skeletal muscle during exercise. Pflugers Arch. 2017;469:1615-1630 pubmed publisher
    ..Trained subjects had higher (P < 0.05) PDH-E1?, PDK1, PDK2, PDK4, and PDP1 protein content as well as PDH phosphorylation and PDH acetylation...
  49. Korotchkina L, Patel M. Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J Biol Chem. 2001;276:37223-9 pubmed
    ..All four PDKs phosphorylated site 1 and site 2, however, with different rates in phosphate buffer (for site 1, PDK2 > PDK4 approximately PDK1 > PDK3; for site 2, PDK3 > PDK4 > PDK2 > PDK1)...
  50. Tuganova A, Popov K. Role of protein-protein interactions in the regulation of pyruvate dehydrogenase kinase activity. Biochem J. 2005;387:147-53 pubmed
  51. Steussy C, Popov K, Bowker Kinley M, Sloan R, Harris R, Hamilton J. Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase. J Biol Chem. 2001;276:37443-50 pubmed
  52. Kobayashi T, Cohen P. 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. Biochem J. 1999;339 ( Pt 2):319-28 pubmed
    ..activation of protein kinase B (PKB) by 3-phosphoinositide-dependent protein kinases-1 and -2 (PDK1 and PDK2 respectively) is a key event in mediating the effects of signals that activate PtdIns 3-kinase...
  53. Kuang X, Liu C, Fang J, Ma W, Zhang J, Cui S. The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development. FEBS Lett. 2016;590:2076-85 pubmed publisher
    ..Inhibition of Pdk2 in lkb1 mutants with dichloroacetate, a promising anticancer drug, rescued the lactate production to wild-type ..
  54. Tuganova A, Boulatnikov I, Popov K. Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex. Biochem J. 2002;366:129-36 pubmed
    ..Binding of PDK1 and PDK2 was readily reversible with the apparent dissociation constant of approx. 10 microM for both isoenzymes...
  55. Sun W, Chang S, Fu Y, Liu Y, Califano J. Chronic CSE treatment induces the growth of normal oral keratinocytes via PDK2 upregulation, increased glycolysis and HIF1? stabilization. PLoS ONE. 2011;6:e16207 pubmed publisher
    ..We demonstrate that chronic CSE treatment upregulates PDK2 expression, decreases PDH activity and thereby increases the glycolytic metabolites pyruvate and lactate...
  56. Tso S, Qi X, Gui W, Wu C, Chuang J, Wernstedt Asterholm I, et al. Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors targeting the ATP-binding pocket. J Biol Chem. 2014;289:4432-43 pubmed publisher
    ..8 ?M for PDK2. The administration of PS10 (70 mg/kg) to diet-induced obese mice significantly augments pyruvate dehydrogenase ..
  57. Jha M, Rahman M, Park D, Kook H, Lee I, Lee W, et al. Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain. J Neurosci Res. 2016;94:837-49 pubmed publisher
    ..a role of PDKs in inflammation and neurometabolic coupling led us to investigate the effect of genetic ablation of PDK2/4 on nociception in a mouse model of acute inflammatory pain...
  58. Gold M, Scheid M, Santos L, Dang Lawson M, Roth R, Matsuuchi L, et al. The B cell antigen receptor activates the Akt (protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase. J Immunol. 1999;163:1894-905 pubmed
    ..We found that BCR engagement induced GSK-3 phosphorylation and decreased GSK-3 enzyme activity. Thus, BCR ligation initiates a PI 3-kinase/Akt/GSK-3 signaling pathway. ..
  59. Fencl F, Janda J, Bláhová K, Hríbal Z, Stekrova J, Puchmajerova A, et al. Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease. Pediatr Nephrol. 2009;24:983-9 pubmed publisher
    ..PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1. ..
  60. Li J, Diao B, Guo S, Huang X, Yang C, Feng Z, et al. VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism. Nat Commun. 2017;8:1322 pubmed publisher
    ..VSIG4 activates the PI3K/Akt-STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/..
  61. Li J, Kato M, Chuang D. Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate. J Biol Chem. 2009;284:34458-67 pubmed publisher
    ..In the present study, we investigated the role of the invariant C-terminal DW-motif in inhibition of human PDK2 by dichloroacetate (DCA)...
  62. Hoefele J, Mayer K, Scholz M, Klein H. Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2011;26:2181-8 pubmed publisher
    ..The increased number of known mutations will facilitate future studies into genotype-phenotype correlations. ..
  63. Contractor T, Harris C. p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2. Cancer Res. 2012;72:560-7 pubmed publisher
    ..Wild-type p53 expression decreased levels of pyruvate dehydrogenase kinase-2 (Pdk2) and the product of its activity, the inactive form of the pyruvate dehydrogenase complex (P-Pdc), both of which ..
  64. Kolobova E, Tuganova A, Boulatnikov I, Popov K. Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites. Biochem J. 2001;358:69-77 pubmed
    ..isoenzymes of protein kinase responsible for the phosphorylation and inactivation of pyruvate dehydrogenase (PDK1, PDK2, PDK3 and PDK4) differ in their abilities to phosphorylate the enzyme...
  65. Leblanc P, Peters S, Tunstall R, Cameron Smith D, Heigenhauser G. Effects of aerobic training on pyruvate dehydrogenase and pyruvate dehydrogenase kinase in human skeletal muscle. J Physiol. 2004;557:559-70 pubmed
    ..3-fold increase in PDK2 isoform protein expression. Similar to 1 week, no changes were observed at the mRNA level after 8 weeks of training...
  66. Neumann H, Jilg C, Bacher J, Nabulsi Z, Malinoc A, Hummel B, et al. Epidemiology of autosomal-dominant polycystic kidney disease: an in-depth clinical study for south-western Germany. Nephrol Dial Transplant. 2013;28:1472-87 pubmed publisher
    ..7/100,000 reaching a maximum of 57.3/100,000 in the 6th decade of life. Prevalence of ADPKD is overestimated by 2- to 5-fold and close to the limit of RDs which may be of broad clinical, logistic and policy implications. ..
  67. Pópulo H, Caldas R, Lopes J, Pardal J, Máximo V, Soares P. Overexpression of pyruvate dehydrogenase kinase supports dichloroacetate as a candidate for cutaneous melanoma therapy. Expert Opin Ther Targets. 2015;19:733-45 pubmed publisher
    ..Our results suggest that PDK expression may play a role in melanoma development and that DCA can be useful for CM therapy, alone or in combination with mTOR inhibitors. ..
  68. Hiromasa Y, Hu L, Roche T. Ligand-induced effects on pyruvate dehydrogenase kinase isoform 2. J Biol Chem. 2006;281:12568-79 pubmed
    Tryptophan fluorescence was used to analyze binding of ligands to human pyruvate dehydrogenase isoform 2 (PDHK2) and to demonstrate effects of ligand binding on distal structure of PDHK2 that is required for binding to the inner lipoyl ..
  69. Hiromasa Y, Yan X, Roche T. 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. 2008;47:2312-24 pubmed publisher
    Association of the PDHK2 and GST-L2 (glutathione-S-transferase fused to the inner lipoyl domain (L2) of dihydrolipoyl acetyltransferase (E2)) dimers was enhanced by K+ with higher affinity K+ binding than occurs at the PDHK2 active site...
  70. Shi G, McQuibban G. The Mitochondrial Rhomboid Protease PARL Is Regulated by PDK2 to Integrate Mitochondrial Quality Control and Metabolism. Cell Rep. 2017;18:1458-1472 pubmed publisher
    ..Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates β cleavage...
  71. Lessmann E, Ngo M, Leitges M, Minguet S, Ridgway N, Huber M. Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and regulates Akt phosphorylation. Cell Signal. 2007;19:384-92 pubmed
    ..Furthermore, mammalian target of rapamycin was implicated in ORP9L phosphorylation in HEK293 cells. These studies identify ORP9 as a PDK-2 substrate and negative regulator of Akt phosphorylation at the PDK-2 site. ..
  72. Gang H, Dhingra R, Lin J, Hai Y, Aviv Y, Margulets V, et al. PDK2-mediated alternative splicing switches Bnip3 from cell death to cell survival. J Cell Biol. 2015;210:1101-15 pubmed publisher
    ..inhibition of the Bnip3Δex3/Bnip3FL isoform ratio by inhibiting pyruvate dehydrogenase kinase isoform 2 (PDK2) in Panc-1 cells rapidly induced mitochondrial perturbations and cell death...
  73. Baker J, Yan X, Peng T, Kasten S, Roche T. Marked differences between two isoforms of human pyruvate dehydrogenase kinase. J Biol Chem. 2000;275:15773-81 pubmed
    ..produces the predominant changes in the rates of phosphorylation of the pyruvate dehydrogenase (E1) component by PDK2 and PDK3...