PDK3

Summary

Gene Symbol: PDK3
Description: pyruvate dehydrogenase kinase, isozyme 3
Alias: CMTX6, pyruvate dehydrogenase kinase, isoenzyme 3, pyruvate dehydrogenase, lipoamide, kinase isozyme 3, mitochondrial
Species: human

Top Publications

  1. pmc Role of the cytoskeleton in muscle transcriptional responses to altered use
    Gretchen A Meyer
    Department of Bioengineering, University of California, San Diego, CA, USA
    Physiol Genomics 45:321-31. 2013
  2. pmc A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene
    Marina L Kennerson
    Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, NSW, Australia
    Hum Mol Genet 22:1404-16. 2013
  3. doi Inactivation of the HIF-1α/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidants
    Jerome 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
  4. doi Pyruvate dehydrogenase E1α phosphorylation is induced by glucose but does not control metabolism-secretion coupling in INS-1E clonal β-cells
    Dmitry Akhmedov
    Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
    Biochim Biophys Acta 1823:1815-24. 2012
  5. pmc Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance
    Chun 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
  6. ncbi Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase
    Lioubov 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
  7. ncbi Molecular and biochemical analysis of phthalate and terephthalate degradation by Rhodococcus sp. strain DK17
    Ki Young Choi
    Department of Biology, Yonsei University, Seoul, Republic of Korea
    FEMS Microbiol Lett 252:207-13. 2005
  8. ncbi Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation
    Gerold Untergasser
    Austrian Academy of Sciences, Institute for Biomedical Aging Research, Rennweg 10, Innsbruck A 6020, Austria
    Mech Ageing Dev 126:59-69. 2005
  9. ncbi R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase
    Lioubov 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
  10. ncbi Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs
    Mary 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

Research Grants

Scientific Experts

  • M C Sugden
  • THOMAS ROCHE
  • David T Chuang
  • DAVID CHUANG
  • Masato Kato
  • Chun Wun Lu
  • Shih Chia Tso
  • Ki Young Choi
  • Lioubov G Korotchkina
  • Jacinta L Chuang
  • Marina L Kennerson
  • Gretchen A Meyer
  • Dmitry Akhmedov
  • Jerome Kluza
  • Emily C Dunford
  • Margriet van Kogelenberg
  • Kirill M Popov
  • Shaw Jenq Tsai
  • Shih Chieh Lin
  • Alina Tuganova
  • Igor Boulatnikov
  • Yancho Devedjiev
  • Tatjana Degenhardt
  • Jong Chan Chae
  • Gerben J Zylstra
  • Dockyu Kim
  • Eungbin Kim
  • Jianxiang Xu
  • Gerold Untergasser
  • Mulchand S Patel
  • Alla Klyuyeva
  • Sukhdeep Sidhu
  • Lawrence L Spriet
  • K M Popov
  • Eppie M Yiu
  • Carolyn Ly
  • Monique M Ryan
  • Gary Rance
  • Martin B Delatycki
  • Alexander P Drew
  • Richard L Lieber
  • Stephan Zuchner
  • Aditi Kidambi
  • Garth A Nicholson
  • Rabia Chaudhry
  • Simon Schenk
  • Patrice Maboudou
  • Laurent Mortier
  • Umberto De Marchi
  • Philippe Marchetti
  • Andreas Wiederkehr
  • Samuel Valable
  • Elisabeth Martin de Lassalle
  • Cyril Maire
  • Claes B Wollheim
  • L G Korotchkina
  • Pierre Formstecher
  • E Kolobova
  • Renata Polakowska
  • Manel Jendoubi
  • Paola Corazao-Rozas
  • Pierre Guerreschi
  • Yasmine Touil
  • Myriam Bernaudin
  • Aurélien Corroyer-Dulmont
  • Myriam Malet-Martino
  • Stéphane Balayssac
  • Caroline Ballot
  • Aurélie Jonneaux
  • Margherita Lerone
  • Joris A Veltman
  • Stephen P Robertson
  • M M Bowker-Kinley
  • William Gittings
  • Sandra J Peters
  • Arjan P M de Brouwer
  • Hans van Bokhoven
  • Rene Vandenboom
  • Maria T Divizia
  • Paul J Leblanc
  • Eric A Herbst
  • Bo Wen Lin
  • Robert A Harris
  • Chung Ta Lee
  • Nam Ho Jeoung
  • Chun Wei Chien
  • Teresa De Toni
  • Jenq Chang Lee
  • Shau Chieh Lin
  • J Greig Inglis

Detail Information

Publications32

  1. pmc Role of the cytoskeleton in muscle transcriptional responses to altered use
    Gretchen 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)...
  2. pmc A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene
    Marina 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...
  3. doi Inactivation of the HIF-1α/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidants
    Jerome 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)...
  4. doi Pyruvate dehydrogenase E1α phosphorylation is induced by glucose but does not control metabolism-secretion coupling in INS-1E clonal β-cells
    Dmitry 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...
  5. pmc Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance
    Chun 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...
  6. ncbi Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase
    Lioubov 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...
  7. ncbi Molecular and biochemical analysis of phthalate and terephthalate degradation by Rhodococcus sp. strain DK17
    Ki 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...
  8. ncbi Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation
    Gerold 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 ..
  9. ncbi R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase
    Lioubov 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)...
  10. ncbi Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs
    Mary 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
    ....
  11. ncbi Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta
    Tatjana 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 ..
  12. pmc Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol
    Masato 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...
  13. ncbi Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase
    L 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...
  14. doi PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensation
    Emily 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...
  15. pmc Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer
    Chun 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 ..
  16. doi A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia
    Margriet 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...
  17. pmc Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites
    E 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...
  18. ncbi Marked differences between two isoforms of human pyruvate dehydrogenase kinase
    J 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 ..
  19. pmc Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex
    M 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. 1998
    Tissue distribution and kinetic parameters for the four isoenzymes of pyruvate dehydrogenase kinase (PDK1, PDK2, PDK3 and PDK4) identified thus far in mammals were analysed...
  20. pmc Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications
    Yancho 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...
  21. ncbi Requirement of duplicated operons for maximal metabolism of phthalate by Rhodococcus sp. strain DK17
    Ki 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...
  22. ncbi Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer
    T 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)...
  23. ncbi Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting
    Lawrence 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...
  24. ncbi Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase
    Igor 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)...
  25. ncbi Therapeutic potential of the mammalian pyruvate dehydrogenase kinases in the prevention of hyperglycaemia
    M 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...
  26. pmc Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex
    Masato 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 ..
  27. pmc Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex
    Alina 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 ..
  28. pmc The carboxy-terminal tail of pyruvate dehydrogenase kinase 2 is required for the kinase activity
    Alla 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 ..
  29. ncbi 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 secretion
    M 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 ..
  30. ncbi Regulation of PDK mRNA by high fatty acid and glucose in pancreatic islets
    Jianxiang 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...
  31. ncbi Structural determinants for cross-talk between pyruvate dehydrogenase kinase 3 and lipoyl domain 2 of the human pyruvate dehydrogenase complex
    Shih 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 ..
  32. ncbi Diversity of the pyruvate dehydrogenase kinase gene family in humans
    R 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...

Research Grants18

  1. Structure and Function of Mitochondrial Protein Kinases
    David T Chuang; Fiscal Year: 2010
    ..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...
  2. Structure and Function of Mitochondrial Protein Kinases
    David T Chuang; Fiscal Year: 2010
    ..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...
  3. Structure and Function of Mitochondrial Protein Kinases
    DAVID CHUANG; Fiscal Year: 2009
    ..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...
  4. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS 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. ..
  5. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2000
    ..Aberrant PDC operation is associated with diabetes and obesity. Inborn errors in components cause severe defects. Primary biliary cirrhosis is an autoimmune disease with antibodies to E2 and other PDC subunits. ..
  6. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 1990
    ....