Genomes and Genes
Gene Symbol: PDK3
Description: pyruvate dehydrogenase kinase 3
Alias: CMTX6, GS1-358P8.4, pyruvate dehydrogenase kinase, isozyme 3, [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial, pyruvate dehydrogenase kinase, isoenzyme 3, pyruvate dehydrogenase, lipoamide, kinase isozyme 3, mitochondrial
- Histone deacetylase inhibitors protect against pyruvate dehydrogenase dysfunction in Huntington's diseaseLuana Naia
CNC Center for Neuroscience and Cell Biology, University of Coimbra UC
J Neurosci . 2017..factor-1 (HIF-1α) stabilization, and decreased the transcription of the two most abundant PDK isoforms, PDK2 and PDK3, culminating in increased PDH activation in mutant cells...
- KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and GlycolysisLing yu Wang
Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USA
Cell Rep 16:3016-27. 2016..The pyruvate dehydrogenase kinases (PDKs) PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial ..
- Pyruvate dehydrogenase kinase regulates hepatitis C virus replicationGwon Soo Jung
Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
Sci Rep 6:30846. 2016..Levels of c-Myc, hypoxia-inducible factor-1α (HIF-1α), PDK1, PDK3, glucokinase, and serine biosynthetic enzymes were compared between HCV-infected and uninfected human liver and Huh-..
- Pathogenic mechanisms underlying X-linked Charcot-Marie-Tooth neuropathy (CMTX6) in patients with a pyruvate dehydrogenase kinase 3 mutationGonzalo Pérez-Siles
Northcott Neuroscience Laboratory, ANZAC Research Institute, University of Sydney, Concord, NSW, Australia Sydney Medical School, University of Sydney, Sydney, NSW, Australia Electronic address
Neurobiol Dis 94:237-44. 2016Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. An X-linked form of CMT (CMTX6) is caused by a missense mutation (R158H) in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene...
- The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndromeMarta Kanabus
Genetics and Genomic Medicine, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
J Inherit Metab Dis 39:415-26. 2016..through increasing ACADVL and CPT1 expression, whilst downregulating genes involved in glucose metabolism (PDK3, PDK4). PCK2, involved in blocking glucose metabolism, was upregulated, as was CAT, encoding catalase...
- GATA4 Regulates Blood-Testis Barrier Function and Lactate Metabolism in Mouse Sertoli CellsAnja Schrade
Children s Hospital A S, A K, O A, M P, M H, University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland Institute of Applied Biotechnology S F, K O, University of Applied Sciences Biberach, Biberach 88400, Germany Metabolomics Unit V V, Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland Departments of Physiology and Pediatrics J T, University of Turku and Turku University Hospital, Turku 20520, Finland and Departments of Pediatrics A S, V M R, D B W, M H and Developmental Biology D B W, Washington University, St Louis, Missouri 63110
Endocrinology 157:2416-31. 2016..Furthermore, Gata4 gene silencing was associated with altered expression of Hk1, Gpi1, Pfkp, Pgam1, Gls2, Pdk3, Pkd4, and Ldhb, genes regulating the production of lactate, a key nutrient that SCs provide to developing germ ..
- X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 geneMarina L Kennerson
Northcott Neuroscience Laboratory, ANZAC Research Institute and Sydney Medical School University of Sydney, Sydney, Australia
J Peripher Nerv Syst 21:45-51. 2016..the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene have been found to cause X-linked dominant CMT type 6 (CMTX6). This study identified the p.R158H PDK3 mutation after screening 67 probable X-linked CMT families...
- Novel molecular mechanisms involved in hormonal regulation of lactate production in Sertoli cellsMariana Regueira
Centro de Investigaciones Endocrinológicas Dr César Bergadá CEDIE CONICET FEI GCBA Hospital de Niños R Gutiérrez, Gallo 1330, C1425EDF Buenos Aires, Argentina
Reproduction 150:311-21. 2015..As for the regulation of PDC, analysis of pyruvate dehydrogenase kinase (Pdk) expression showed that FSH increases Pdk3 and decreases Pdk4 mRNA levels while bFGF increases the expression of all Pdks...
- Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturationXiaojing Hou
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China
J Cell Sci 128:2319-29. 2015..We found that PDK3-mediated phosphorylation of Ser293-PDHE1α results in disruption of meiotic spindle morphology and chromosome ..
- HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2Alessandro Prigione
Molecular Embryology and Ageing Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany Department of Neuroproteomics, Max Delbrueck Center for Molecular Medicine MDC, Berlin, Germany
Stem Cells 32:364-76. 2014..activation appears critical in the early upregulation of other HIF1α-associated metabolic regulators, including PDK3 and pyruvate kinase (PK) isoform M2 (PKM2), resulting in increased glycolysis and enhanced reprogramming...
- Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complexJean Marc Blouin
INSERM UMR S 747, Universite Paris Descartes, Centre Universitaire des Saints Peres, Paris, France
Int J Cancer 128:2591-601. 2011....
- Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistanceChun Wun Lu
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 701, Taiwan
J Biol Chem 283:28106-14. 2008..Herein, we reported that hypoxia-inducible factor-1 (HIF-1) induced pyruvate dehydrogenase kinase-3 (PDK3) expression leading to inhibition of mitochondrial respiration...
- Pyruvate dehydrogenase E1α phosphorylation is induced by glucose but does not control metabolism-secretion coupling in INS-1E clonal β-cellsDmitry Akhmedov
Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Biochim Biophys Acta 1823:1815-24. 2012..In INS-1E cells, suppression of the two main isoforms, PDK1 and PDK3, almost completely prevented PDH E1α phosphorylation...
- Inactivation of the HIF-1α/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidantsJerome Kluza
Unit 837 Equipe 4 Inserm and Faculté de Médecine, Université de Lille II 1 Place, Verdun Cedex, CHRU Lille, France
Cancer Res 72:5035-47. 2012..and promoted mitochondrial respiration via specific reduction in the expression of pyruvate dehydrogenase kinase-3 (PDK3)...
- Characterization of testis-specific isoenzyme of human pyruvate dehydrogenaseLioubov G Korotchkina
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York 14214, USA
J Biol Chem 281:9688-96. 2006..mechanism of inactivation by phosphorylation of three sites; and (iv) in the phosphorylation of sites 1 and 2 by PDK3. In contrast, the differences for PDH2 were indicated as follows: (i) by a 2...
- A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) geneMarina L Kennerson
Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, NSW, Australia
Hum Mol Genet 22:1404-16. 2013..G473A (p.R158H) in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. The change localized within the 1...
- Molecular and biochemical analysis of phthalate and terephthalate degradation by Rhodococcus sp. strain DK17Ki Young Choi
Department of Biology, Yonsei University, Seoul, Republic of Korea
FEMS Microbiol Lett 252:207-13. 2005..In addition to two known plasmids (380-kb pDK1 and 330-kb pDK2), a third megaplasmid (750-kb pDK3) was newly identified in DK17...
- Role of the cytoskeleton in muscle transcriptional responses to altered useGretchen A Meyer
Department of Bioengineering, University of California, San Diego, CA, USA
Physiol Genomics 45:321-31. 2013..many genes related to slow fiber pathway (Myh7, Myl3, Atp2a2, and Casq2) and insulin sensitivity (Tlr4, Trib3, Pdk3, and Pdk4)...
- Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiationGerold Untergasser
Austrian Academy of Sciences, Institute for Biomedical Aging Research, Rennweg 10, Innsbruck A 6020, Austria
Mech Ageing Dev 126:59-69. 2005..Pyruvate dehydrogenase kinase 3 (Pdk3) and connective tissue growth factor (Ctgf) were up-regulated and hyaluronan synthase 3 (Has3) down-regulated under ..
- R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinaseLioubov G Korotchkina
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA
Free Radic Res 38:1083-92. 2004..affect activities of PDPs and at the same time inhibited PDKs to different extents (PDK1>PDK4 approximately PDK2>PDK3 for R-LA)...
- A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopiaMargriet van Kogelenberg
Department of Paediatrics and Child Health, Dunedin School of Medicine, Otago University, Dunedin, New Zealand
Am J Med Genet A 155:3144-7. 2011..11 affecting all or part of three annotated genes, ZFX, PDK3, and PCYT1B in this subject...
- Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancerChun Wun Lu
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Am J Pathol 179:1405-14. 2011..Pyruvate dehydrogenase kinase-1 (PDK1) and PDK3 participate in the metabolic switch of cancer cells; however, the medical significance of PDK1 and PDK3 in cancer ..
- PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensationEmily C Dunford
Centre for Muscle Metabolism and Biophysics, Brock University, St Catharines, Ontario, Canada
Am J Physiol Regul Integr Comp Physiol 300:R1487-93. 2011..PDH is deactivated by a set of PDH kinases (PDK1, PDK2, PDK3, PDK4), with PDK2 and PDK4 being the most predominant isoforms in skeletal muscle...
- Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implicationsYancho Devedjiev
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, School of Medicine and Dentistry, Kaul Genetics Building, Birmingham, AL 35294, USA
J Mol Biol 370:407-16. 2007..Thus, the L2-domains likely act not only as the structural anchors but also modulate the catalytic cycle of PDHK...
- Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fastingLawrence L Spriet
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1
J Appl Physiol (1985) 96:2082-7. 2004..The changes in PDK-4 expression and PDH activity did not coincide with increases in the transcriptional activators PPAR-alpha and FKHR...
- Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complexM M Bowker-Kinley
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202 5122, USA
Biochem J 329:191-6. 1998Tissue distribution and kinetic parameters for the four isoenzymes of pyruvate dehydrogenase kinase (PDK1, PDK2, PDK3 and PDK4) identified thus far in mammals were analysed...
- Marked differences between two isoforms of human pyruvate dehydrogenase kinaseJ C Baker
Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
J Biol Chem 275:15773-81. 2000..the predominant changes in the rates of phosphorylation of the pyruvate dehydrogenase (E1) component by PDK2 and PDK3. E2 assembles as a 60-mer via its C-terminal domain and has mobile connections to an E1-binding domain and then two ..
- Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sitesE Kolobova
Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri Kansas City, Kansas City, MO 64110 2499, USA
Biochem J 358:69-77. 2001..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...
- Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenaseL G Korotchkina
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York 14214, USA
J Biol Chem 276:37223-9. 2001..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). Site 3 was phosphorylated by PDK1 only...
- Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretionM C Sugden
Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, St Bartholomew s and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London, U K
Diabetes 50:2729-36. 2001..study, using antibodies against PDK1, PDK2, and PDK4 (no sufficiently specific antibodies are as yet available for PDK3), we identified the PDK isoform profile of the pancreatic islet and delineated the effects of starvation (48 h) on ..
- Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complexAlina Tuganova
Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri Kansas City, Kansas City, MO 64110 2499, U S A
Biochem J 366:129-36. 2002..It was found that PDK isoenzymes are markedly different with respect to their affinities for L2. PDK3 demonstrated a very tight binding, which persisted during isolation of PDK3-L2 complexes using size-exclusion ..
- Therapeutic potential of the mammalian pyruvate dehydrogenase kinases in the prevention of hyperglycaemiaM C Sugden
Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, St Bartholomew s and Royal London School of Medicine and Dentistry, Queen Mary, University of London, London E1 4NS, U K
Curr Drug Targets Immune Endocr Metabol Disord 2:151-65. 2002..in most major tissues and organs of the body, PDK1 appears to be limited to the heart and pancreatic islets, and PDK3 is limited to the kidney, brain and testis...
- Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinaseIgor Boulatnikov
Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri Kansas City, 5110 Rockhill Road, Kansas City, MO 64110 2499, USA
Biochim Biophys Acta 1645:183-92. 2003..genetically and biochemically distinct forms of PDK that are expressed in a tissue-specific manner (PDK1, PDK2, PDK3, and PDK4)...
- Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKsMary C Sugden
Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, Bart s and The London, Queen Mary s School of Medicine and Dentistry, University of London, Mile End Road, London E1 4NS, United Kingdom
Am J Physiol Endocrinol Metab 284:E855-62. 2003....
- Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicolMasato Kato
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Structure 15:992-1004. 2007..We have determined structures of human PDK1 or PDK3 bound to the inhibitors AZD7545, dichloroacetate (DCA), and radicicol...
- Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complexMasato Kato
Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
EMBO J 24:1763-74. 2005..b>PDK3 binds to the inner lipoyl domains (L2) from the 60-meric transacetylase (E2p) core of PDC, with concomitant ..
- The carboxy-terminal tail of pyruvate dehydrogenase kinase 2 is required for the kinase activityAlla Klyuyeva
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama, Birmingham, Alabama 35294, USA
Biochemistry 44:13573-82. 2005..We also show that the carboxyl tails derived from isozymes PDK1, PDK3, and PDK4 are capable of supporting the kinase activity of the kinase core derived from PDK2 as well as binding of ..
- Regulation of PDK mRNA by high fatty acid and glucose in pancreatic isletsJianxiang Xu
Kosair Children s Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40292, USA
Biochem Biophys Res Commun 344:827-33. 2006..The gene and protein for PDK3 were not expressed in islets. Palmitate up-regulated mRNA expression of PDK1 (2.9-fold), PDK2 (1...
- Structural determinants for cross-talk between pyruvate dehydrogenase kinase 3 and lipoyl domain 2 of the human pyruvate dehydrogenase complexShih Chia Tso
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
J Biol Chem 281:27197-204. 2006..We showed previously that binding of the lipoyl domain 2 (L2) of the pyruvate dehydrogenase complex to PDK3 induces a "cross-tail" conformation in PDK3, resulting in an opening of the active site cleft and the stimulation ..
- Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancerT E Roche
Department of Biochemistry, Kansas State University, Chalmers Hall, Manhattan, KS 66506, USA
Cell Mol Life Sci 64:830-49. 2007..complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4)...
- Requirement of duplicated operons for maximal metabolism of phthalate by Rhodococcus sp. strain DK17Ki Young Choi
Department of Biology, Yonsei University, Seoul 120 749, Republic of Korea
Biochem Biophys Res Commun 357:766-71. 2007..of phthalate to protocatechuate are duplicated and present on two different megaplasmids [pDK2 (330 kb) and pDK3 (750 kb)] in Rhodococcus sp. strain DK17...
- Diversity of the pyruvate dehydrogenase kinase gene family in humansR Gudi
Department of Biochemistry and Molecular Biology, Indiana University, School of Medicine, Indianapolis 46202 5122, USA
J Biol Chem 270:28989-94. 1995..primary structures, two isoenzymes identified in humans correspond to rat PDK1 and PDK2, whereas a third gene (PDK3) encodes for a new isoenzyme that shares 68% and 67% of amino acid identities with PDK1 and PDK2, respectively...
- Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/deltaTatjana Degenhardt
Department of Biochemistry, University of Kuopio, FIN 70211, Kuopio, Finland
J Mol Biol 372:341-55. 2007..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 are ..
- David T Chuang; Fiscal Year: 2016..I.'s laboratory has solved the crystal structures for three (PDK1, PDK3 and PDK4) of the four PDK isoforms and various PDK-inhibitor/activator complexes. Based on these advances, the P.I...
- REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASETHOMAS ROCHE; Fiscal Year: 2004..The long term objective is to understand the tissue-specific control of PDC and to delineate the unique properties of kinase isoforms overexpressed in diabetes which inactivates PDC thereby minimize glucose use. ..