PDK1

Summary

Gene Symbol: PDK1
Description: pyruvate dehydrogenase kinase, isozyme 1
Alias: PDH kinase 1, [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial, mitochondrial pyruvate dehydrogenase, lipoamide, kinase isoenzyme 1, pyruvate dehydrogenase kinase, isoenzyme 1
Species: human

Top Publications

  1. ncbi Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERK
    S A Richards
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Curr Biol 9:810-20. 1999
  2. pmc Analysis of 3-phosphoinositide-dependent kinase-1 signaling and function in ES cells
    Tanja Tamguney
    UCSF Cancer Research Institute, USA
    Exp Cell Res 314:2299-312. 2008
  3. ncbi Pancreatic beta cell mass preserved in heterozygous PDK1 knockout mice
    Akihiko Takeda
    Department of Internal Medicine, Division of Diabetes, Metabolism, and Endocrinology, Kobe University Graduate School of Medicine, Kobe 17, Japan
    Kobe J Med Sci 54:E183-90. 2008
  4. ncbi HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia
    Jung whan Kim
    Graduate Program of Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell Metab 3:177-85. 2006
  5. pmc Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1
    Jung whan Kim
    Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mol Cell Biol 27:7381-93. 2007
  6. pmc Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 111:3723-34. 2008
  7. pmc Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha
    K S Walker
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, Scotland, U K
    Biochem J 331:299-308. 1998
  8. doi Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis
    Anne Vejux
    INSERM U866, Faculte des Sciences Gabriel, 6 Bd Gabriel, 21000 Dijon, France
    J Nutr Biochem 20:45-61. 2009
  9. ncbi p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1)
    C C King
    Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 275:41201-9. 2000
  10. ncbi 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1
    C J Jensen
    Department of Clinical Biochemistry, Glostrup Hospital, DK 2600 Glostrup, Denmark
    J Biol Chem 274:27168-76. 1999

Research Grants

  1. PPAR-delta in obesity-related vascular remodeling
    Yuqing Chen; Fiscal Year: 2004
  2. Insulin Signaling in a Cell-Free System
    Michael Mueckler; Fiscal Year: 2007
  3. Human Skeletal Muscle Proteome and Phosphoproteome in Obesity and Type 2 Diabetes
    ZhengPing Yi; Fiscal Year: 2010
  4. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2010
  5. Protein Kinase - Primary Structure and cAMP Interaction
    Susan S Taylor; Fiscal Year: 2011
  6. Protein Kinase - Primary Structure and cAMP Interaction
    Susan S Taylor; Fiscal Year: 2010
  7. Hepatitis C: E2 Molecular Mechanisms
    Martina Buck; Fiscal Year: 2010
  8. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2009
  9. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2009
  10. Membrane Rafts and Sertoli-Germ Cell Interactions
    SALLY NYQUIST; Fiscal Year: 2002

Detail Information

Publications161 found, 100 shown here

  1. ncbi Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERK
    S A Richards
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Curr Biol 9:810-20. 1999
    ..It is thought that stimulation of the ERK/MAP kinase pathway is sufficient for RSK1 activation, but how ERK phosphorylation activates the RSK1 amino-terminal kinase domain is not known...
  2. pmc Analysis of 3-phosphoinositide-dependent kinase-1 signaling and function in ES cells
    Tanja Tamguney
    UCSF Cancer Research Institute, USA
    Exp Cell Res 314:2299-312. 2008
    3-phosphoinositide-dependent kinase-1 (PDK1) phosphorylates and activates several kinases in the cAMP-dependent, cGMP-dependent and protein kinase C (AGC) family...
  3. ncbi Pancreatic beta cell mass preserved in heterozygous PDK1 knockout mice
    Akihiko Takeda
    Department of Internal Medicine, Division of Diabetes, Metabolism, and Endocrinology, Kobe University Graduate School of Medicine, Kobe 17, Japan
    Kobe J Med Sci 54:E183-90. 2008
    We have demonstrated that 3-phosphoinositide-dependent protein kinase 1 (PDK1) contributes to signaling by insulin or insulin-like growth factor-1 (IGF-1) that is responsible for the regulation of both the number and size of pancreatic ..
  4. ncbi HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia
    Jung whan Kim
    Graduate Program of Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell Metab 3:177-85. 2006
    ..the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA...
  5. pmc Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1
    Jung whan Kim
    Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mol Cell Biol 27:7381-93. 2007
    ....
  6. pmc Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 111:3723-34. 2008
    ..Finally, BAG956 and rapamycin/RAD001 were shown to combine in a nonantagonistic fashion against BCR-ABL- and mutant FLT3-expressing cells both in vitro and in vivo...
  7. pmc Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha
    K S Walker
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, Scotland, U K
    Biochem J 331:299-308. 1998
    ..phosphorylated at similar rates and activated to similar extents by 3-phosphoinositide-dependent protein kinase-1 (PDK1)...
  8. doi Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis
    Anne Vejux
    INSERM U866, Faculte des Sciences Gabriel, 6 Bd Gabriel, 21000 Dijon, France
    J Nutr Biochem 20:45-61. 2009
    ..Thus, 7KC-induced apoptosis is a PI3-K-dependent event, and Vit-E up- and down-regulates PI3-K activity and phospholipidosis, respectively...
  9. ncbi p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1)
    C C King
    Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 275:41201-9. 2000
    In this study, we show that phosphorylated 3-phosphoinositide-dependent kinase 1 (PDK1) phosphorylates p21-activated kinase 1 (PAK1) in the presence of sphingosine...
  10. ncbi 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1
    C J Jensen
    Department of Clinical Biochemistry, Glostrup Hospital, DK 2600 Glostrup, Denmark
    J Biol Chem 274:27168-76. 1999
    ..Here, we show that the isolated N-terminal kinase of RSK2 (amino acids 1-360) is phosphorylated at Ser(227) by PDK1, a constitutively active kinase, leading to 100-fold stimulation of kinase activity...
  11. ncbi Regulation of kinase activity of 3-phosphoinositide-dependent protein kinase-1 by binding to 14-3-3
    Saori Sato
    Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan
    J Biol Chem 277:39360-7. 2002
    3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a central role in activating the protein kinase A, G, and C subfamily...
  12. 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
    ....
  13. ncbi Sphingosine is a novel activator of 3-phosphoinositide-dependent kinase 1
    C C King
    Departments of Immunology, Cell Biology, and Chemistry and the Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 275:18108-13. 2000
    3-Phosphoinositide-dependent kinase 1 (PDK1) has previously been shown to phosphorylate the activation loop of several AGC kinase family members...
  14. doi Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1
    Ayaz Najafov
    University of Dundee, Scotland, UK
    Biochem J 433:357-69. 2011
    b>PDK1 (3-phosphoinositide-dependent protein kinase 1) activates a group of protein kinases belonging to the AGC [PKA (protein kinase A)/PKG (protein kinase G)/PKC (protein kinase C)]-kinase family that play important roles in mediating ..
  15. ncbi Evidence that 3-phosphoinositide-dependent protein kinase-1 mediates phosphorylation of p70 S6 kinase in vivo at Thr-412 as well as Thr-252
    A Balendran
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, Scotland
    J Biol Chem 274:37400-6. 1999
    ..of PKBalpha and Thr-252 of p70 S6 kinase are phosphorylated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) in vitro...
  16. doi mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 416:375-85. 2008
    ..b>PDK1 (phosphoinositide-dependent kinase 1) phosphorylates the T-loop of SGK1...
  17. ncbi Characterization of PDK2 activity against protein kinase B gamma
    Conrad P Hodgkinson
    Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, United Kingdom
    Biochemistry 41:10351-9. 2002
    ..b>PDK1 has clearly been shown to phosphorylate the threonine, but the mechanism leading to phosphorylation of the serine, ..
  18. pmc Mechanism of PDK1-catalyzed Thr-229 phosphorylation of the S6K1 protein kinase
    Malik M Keshwani
    Department of Chemistry, University of Miami, Coral Gables, Florida 33124, USA
    J Biol Chem 284:22611-24. 2009
    b>PDK1 (phosphoinositide-dependent protein kinase-1) catalyzes phosphorylation of Thr-229 in the T-loop of S6K1 alpha II (the 70-kDa 40 S ribosomal protein S6 kinase-1 alpha II isoform), and Thr-229 phosphorylation is synergistic with C-..
  19. pmc Baculovirus-mediated expression, purification, and characterization of a fully activated catalytic kinase domain construct of the 70 kDa 40S ribosomal protein S6 kinase-1 alphaII isoform (S6K1alphaII)
    Malik M Keshwani
    Department of Chemistry, University of Miami, P O Box 249118, Coral Gables, FL 33124 0431, USA
    Protein Expr Purif 58:32-41. 2008
    ..single mutant isoform, which was in vitro phosphorylated by the upstream T229 kinase, PDK1 ( approximately 75 nmol/min/mg)...
  20. pmc 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
    T Kobayashi
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, MSI WTB complex, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 339:319-28. 1999
    ..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...
  21. ncbi 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase
    D R Alessi
    Department of Biochemistry, University of Dundee, UK
    Curr Biol 7:776-89. 1997
    ..We recently identified a protein kinase, termed PDK1, that phosphorylates PKB at Thr308 only in the presence of lipid vesicles containing phosphatidylinositol 3,4,5-..
  22. 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...
  23. ncbi Regulation of protein kinase Mzeta synthesis by multiple kinases in long-term potentiation
    Matthew Taylor Kelly
    Department of Physiology, The Robert F Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA
    J Neurosci 27:3439-44. 2007
    ..however, PKMzeta must be phosphorylated on its activation loop by phosphoinositide-dependent protein kinase-1 (PDK1) for optimal catalytic activity...
  24. ncbi PDK1 and PKB/Akt: ideal targets for development of new strategies to structure-based drug design
    Thomas K Harris
    University of Miami School of Medicine, Department of Biochemistry and Molecular Biology R 629, PO Box 016129, Miami, FL 33101 6129, USA
    IUBMB Life 55:117-26. 2003
    ..PI(3,4)P2] and PI(3,4,5)P3, which mediate membrane translocation of the phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (PKB, also known as Akt)...
  25. ncbi Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells
    Luciano Pirola
    INSERM U145, IFR50, Faculte de Medecine, 06107 Nice Cedex 2, France
    J Biol Chem 278:15641-51. 2003
    ..b>PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase ..
  26. pmc Fluorescence resonance energy transfer in quantum dot-protein kinase assemblies
    Ibrahim Yildiz
    Center for Supramolecular Science, Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146 0431, USA
    J Biomed Biotechnol 2007:18081. 2007
    ..we have designed a binding assay to probe the interactions of human phosphoinositide-dependent protein kinase-1 (PDK1) with potential ligands...
  27. pmc Reconstitution of modular PDK1 functions on trans-splicing of the regulatory PH and catalytic kinase domains
    Hassan Al-Ali
    Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33101 6129, USA
    Bioconjug Chem 18:1294-302. 2007
    The serine-threonine protein kinases PDK1 and PKB each contain a pleckstrin homology (PH) domain that binds the membrane-bound phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P3] second messenger and is required for PDK1-catalyzed ..
  28. ncbi Reduced Ca2+ entry and suicidal death of erythrocytes in PDK1 hypomorphic mice
    Michael Foller
    Department of Physiology, University of Tuebingen, Gmelinstr 5, 72076 Tubingen, Germany
    Pflugers Arch 455:939-49. 2008
    The phosphoinositide-dependent kinase PDK1 is a key element in the phosphoinositol-3-kinase signalling pathway, which is involved in the regulation of ion channels, transporters, cell volume and cell survival...
  29. ncbi Phase I trial of UCN-01 in combination with topotecan in patients with advanced solid cancers: a Princess Margaret Hospital Phase II Consortium study
    S J Hotte
    Princess Margaret Hospital Phase II Consortium, Cancer Therapy Evaluation Program, and National Cancer Institute, Bethesda, MD, USA
    Ann Oncol 17:334-40. 2006
    ..kinases including the Ca2+ and phospholipid-dependent protein kinase C (PKC), CDKs 2, 4, 6, Chk-1 and PDK1. UCN-01 mediates distinct effects in vitro/in vivo: cell cycle arrest in G1, abrogation of G2 arrest by inhibiting ..
  30. pmc Activation of the PI3K/Akt pathway early during vaccinia and cowpox virus infections is required for both host survival and viral replication
    Jamária A P Soares
    Grupo de Transdução de Sinal, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 31270 901 Belo Horizonte, Minas Gerais, Brazil
    J Virol 83:6883-99. 2009
    ..target of rapamycin complex 2 (mTORC2), which was paralleled by phosphorylation at T308 [Akt(T308-P)] by PI3K/PDK1, which is required for host survival...
  31. doi The survival pathways phosphatidylinositol-3 kinase (PI3-K)/phosphoinositide-dependent protein kinase 1 (PDK1)/Akt modulate liver regeneration through hepatocyte size rather than proliferation
    Sanae Haga
    Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan
    Hepatology 49:204-14. 2009
    ..The current study was designed to investigate the roles of phosphoinositide-dependent protein kinase 1 (PDK1)-associated pathways in liver regeneration after partial hepatectomy (PH) using liver-specific Pdk1-knockout (L-..
  32. doi Role of PDK1 in regulation of gastric acid secretion
    Anand Rotte
    Department of Physiology, University of Tubingen, Tubingen, Germany
    Cell Physiol Biochem 22:725-34. 2008
    ..Signaling of PI-3-kinase includes activation of the phosphoinositide dependent kinase PDK1. We thus hypothesized that PDK1 may influence gastric acid secretion...
  33. pmc Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase
    T Kobayashi
    MRC Protein Phosphorylation Unit, Department of Biochemistry, MSI WTB complex, Dow Street, University of Dundee, Dundee DD1 5EH, Scotland, U K
    Biochem J 344:189-97. 1999
    ..with protein kinase B (PKB) and, like PKB, is activated in vitro by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and in vivo in response to signals that activate phosphatidylinositol (PI) 3-kinase...
  34. ncbi Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidation
    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 at Queen Mary and Westfield College, London E1 4NS, UK
    J Endocrinol 167:339-45. 2000
    The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC)...
  35. pmc Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast
    S Friant
    Biozentrum of the University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    EMBO J 20:6783-92. 2001
    ..one of the two kinases Pkh1p or Pkh2p, that are homologous to mammalian 3-phosphoinositide-dependent kinase-1 (PDK1), can specifically suppress the sphingoid base synthesis requirement for endocytosis...
  36. ncbi Regulation and physiological roles of serum- and glucocorticoid-induced protein kinase isoforms
    F Lang
    Department of Physiology, University of Tubingen, Germany
    Sci STKE 2001:re17. 2001
    ..stimulate phosphatidylinositol 3-kinase, and this is mediated by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and another protein kinase that has yet to be identified...
  37. ncbi Insulin receptor substrate-2 phosphorylation is necessary for protein kinase C zeta activation by insulin in L6hIR cells
    F Oriente
    Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II University of Naples, 80131 Italy
    J Biol Chem 276:37109-19. 2001
    ..b>PDK1 (a phosphatidylinositol trisphosphate-dependent kinase) and Akt/protein kinase B (PKB) activation by insulin showed ..
  38. pmc Identification of calcium-regulated heat-stable protein of 24 kDa (CRHSP24) as a physiological substrate for PKB and RSK using KESTREL
    Gillian C Auld
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 389:775-83. 2005
    ..a similar phosphorylation of CRHSP24 in ES (embryonic stem) cells from wild-type mice or mice that express the PDK1 (3-phosphoinositide-dependent kinase 1) mutant (PDK1[L155E]) that activates PKBalpha normally, but cannot activate ..
  39. ncbi Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration
    David S Weber
    Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA 30322, USA
    Circ Res 94:1219-26. 2004
    ..the Src- and Rac-effector p21-activated protein kinase (PAK) 1 on Thr423 (the phosphoinositide-dependent kinase-1 [PDK1] site) was attenuated by ROS inhibition, and infection of VSMCs with dominant-negative PAK1 adenovirus attenuated ..
  40. pmc Regulation of gastric acid secretion by PKB/Akt2
    Anand Rotte
    Department of Physiology, University of Tubingen, D 72076 Tubingen, Germany
    Cell Physiol Biochem 25:695-704. 2010
    ..inhibition of phosphoinositol 3 kinase (PI3K) and partial deficiency of phosphoinositide dependent kinase PDK1 have previously been shown to enhance basal gastric acid secretion...
  41. ncbi Identification of tyrosine phosphorylation sites on 3-phosphoinositide-dependent protein kinase-1 and their role in regulating kinase activity
    J Park
    Friedrich Miescher Institute, Maulbeerstrasse 66, Basel CH 4058, Switzerland
    J Biol Chem 276:37459-71. 2001
    3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a central role in signal transduction pathways that activate phosphoinositide 3-kinase...
  42. pmc Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure
    Alfonso Mora
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 385:639-48. 2005
    The liver plays an important role in insulin-regulated glucose homoeostasis. To study the function of the PDK1 (3-phosphoinositide-dependent protein kinase-1) signalling pathway in mediating insulin's actions in the liver, we employed CRE ..
  43. doi Potential inhibition of PDK1/Akt signaling by phenothiazines suppresses cancer cell proliferation and survival
    Jang Hyun Choi
    Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea
    Ann N Y Acad Sci 1138:393-403. 2008
    3'-Phosphoinositide-dependent kinase-1 (PDK1) has been identified for its ability to phosphorylate and activate Akt...
  44. ncbi Receptor association and tyrosine phosphorylation of S6 kinases
    Heike Rebholz
    Ludwig Institute for Cancer Research, London, UK
    FEBS J 273:2023-36. 2006
    ..and is mainly mediated via phosphatidylinositol 3-kinase (PI3K)-3-phosphoinositide-dependent protein kinase-1 (PDK1) and mTor-dependent pathways...
  45. ncbi Leflunomide inhibits PDK1/Akt pathway and induces apoptosis of human mast cells
    Norifumi Sawamukai
    First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
    J Immunol 179:6479-84. 2007
    ..evident for the first time that the mechanism involved in this result was the concentration-dependent inhibition of PDK1 phosphorylation, which controls the activation of Akt...
  46. pmc PDK1 and HR46 gene homologs tie social behavior to ovary signals
    Ying Wang
    School of Life Sciences, Arizona State University, Tempe, AZ, USA
    PLoS ONE 4:e4899. 2009
    ..Our data show for the first time that the activity of two positional candidate genes for behavior, PDK1 and HR46, have direct genetic relationships to ovary size, a central reproductive trait that correlates with the ..
  47. pmc WNK1, the kinase mutated in an inherited high-blood-pressure syndrome, is a novel PKB (protein kinase B)/Akt substrate
    Alberto C Vitari
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 378:257-68. 2004
    ..Moreover, IGF1-induced phosphorylation of endogenous WNK1 did not occur in PDK1-/- ES (embryonic stem) cells, in which PKB is not activated...
  48. 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
    Pyruvate dehydrogenase kinase isoforms (PDK1-4) are the molecular switch that down-regulates activity of the human pyruvate dehydrogenase complex through reversible phosphorylation...
  49. ncbi Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells
    Emily L Abbot
    Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, UK
    FEBS J 272:3004-14. 2005
    ..The identification of multiple isoforms of pyruvate dehydrogenase kinase (PDK1-4) and pyruvate dehydrogenase phosphatase (PDP1-2) has raised intriguing new possibilities for chronic pyruvate ..
  50. pmc Reciprocal control of pyruvate dehydrogenase kinase and phosphatase by inositol phosphoglycans. Dynamic state set by "push-pull" system
    Patricia McLean
    Division of Infection and Immunity, University College London Medical School, London W1T 4JF, United Kingdom
    J Biol Chem 283:33428-36. 2008
    ..inactive) forms controlled by pyruvate dehydrogenase phosphatases (PDP1,2) and pyruvate dehydrogenase kinases (PDK1-4)...
  51. pmc Selective disruption of insulin-like growth factor-1 (IGF-1) signaling via phosphoinositide-dependent kinase-1 prevents the protective effect of IGF-1 on human cancer cell death
    A Teresa Alberobello
    Dipartimento di Biologia e Patologia Cellulare e Molecolare and Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Universita di Napoli Federico II, 80131 Naples, Italy
    J Biol Chem 285:6563-72. 2010
    ..rapidly and transiently induced tyrosine phosphorylation and activation of phosphoinositide-dependent kinase-1 (PDK1)...
  52. pmc 3-phosphoinositide-dependent protein kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases
    Zhihui Xie
    Department of Oncology, Georgetown University School of Medicine, and Lombardi Comprehensive Cancer Center, Washington, DC, USA
    BMC Cancer 6:77. 2006
    ..b>PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor ..
  53. ncbi In vivo role of the phosphate groove of PDK1 defined by knockin mutation
    Barry J Collins
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee, DD1 5EH, UK
    J Cell Sci 118:5023-34. 2005
    ..activated following phosphorylation at their T-loop residue by the 3-phosphoinositide-dependent protein kinase-1 (PDK1)...
  54. ncbi Role of PDK1 in insulin-signaling pathway for glucose metabolism in 3T3-L1 adipocytes
    Tetsuya Yamada
    Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, 980 8574, Japan
    Am J Physiol Endocrinol Metab 282:E1385-94. 2002
    To investigate the role of 3-phosphoinositide-dependent protein kinase 1 (PDK1) in the insulin-signaling pathway for glucose metabolism, wild-type (wt), the kinase-dead (kd), or the plecstrin homology (PH) domain deletion (DeltaPH) mutant ..
  55. pmc Chemotactic activation of Dictyostelium AGC-family kinases AKT and PKBR1 requires separate but coordinated functions of PDK1 and TORC2
    Xin Hua Liao
    Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892 8028, USA
    J Cell Sci 123:983-92. 2010
    ..AKT and PKBR1 are phosphorylated at similar sites by phosphoinositide-dependent kinase 1 (PDK1) and TORC2 kinases; however, they have different subcellular localizing domains...
  56. doi Activation of the cardiac mTOR/p70(S6K) pathway by leucine requires PDK1 and correlates with PRAS40 phosphorylation
    Cossette Sanchez Canedo
    Universite Catholique de Louvain, Brussels, Belgium
    Am J Physiol Endocrinol Metab 298:E761-9. 2010
    ..via the canonical association of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent protein kinase-1 (PDK1), and protein kinase B (PKB/Akt)...
  57. doi Combined 3D-QSAR modeling and molecular docking study on indolinone derivatives as inhibitors of 3-phosphoinositide-dependent protein kinase-1
    Mohamed Diwan M Abdulhameed
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky 40536, USA
    J Chem Inf Model 48:1760-72. 2008
    3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for developing novel anticancer drugs...
  58. pmc 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma
    Matthew Maurer
    Department of Medicine and Pathology, Herbert Irving Comprehensive Cancer Center, Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Cancer Res 69:6299-306. 2009
    ..3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT...
  59. ncbi Protein kinase C(mu) regulation of the JNK pathway is triggered via phosphoinositide-dependent kinase 1 and protein kinase C(epsilon)
    Ilona Brändlin
    Fraunhofer Institute for Interfacial Engineering, Nobelstrabetae 12, 70569 Stuttgart, Germany
    J Biol Chem 277:45451-7. 2002
    ..PKC(mu) colocalizes with PKC(epsilon) in HEK293 and MCF7 cells as shown by confocal immunofluorescence analyses. PDK1, known as the upstream kinase for several PKC isozymes, associates intracellularly with PKC(epsilon) and PKC(eta)...
  60. doi Pdk1 kinase regulates basal disease resistance through the OsOxi1-OsPti1a phosphorylation cascade in rice
    Hidenori Matsui
    Division of Plant Sciences, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, 305 8602 Japan
    Plant Cell Physiol 51:2082-91. 2010
    ..In eukaryotes, AGC kinase family proteins are regulated by 3-phosphoinositide-dependent protein kinase 1 (Pdk1)...
  61. ncbi Impaired intestinal NHE3 activity in the PDK1 hypomorphic mouse
    Ciprian Sandu
    Department of Physiology I, University of Tubingen, Germany
    Am J Physiol Gastrointest Liver Physiol 291:G868-76. 2006
    ..The present study was performed to explore the role of PDK1 in the regulation of NHE3 activity...
  62. ncbi The Arabidopsis protein kinase PTI1-2 is activated by convergent phosphatidic acid and oxidative stress signaling pathways downstream of PDK1 and OXI1
    Richard G Anthony
    School of Biological Sciences, Royal Holloway, University of London, Egham Hill, Egham, Surrey TW20 0EX, United Kingdom
    J Biol Chem 281:37536-46. 2006
    Arabidopsis PDK1 activity is regulated by binding to the lipid phosphatidic acid (PA) resulting in activation of the oxidative stress-response protein kinase OXI1/AGC2-1...
  63. pmc Requirement of 3-phosphoinositide-dependent protein kinase-1 for BDNF-mediated neuronal survival
    Giorgi Kharebava
    Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, Kentucky 40292, USA
    J Neurosci 28:11409-20. 2008
    Although PDK1 regulates several signaling pathways that respond to neurotrophins, direct evidence for its involvement in neurotrophin-mediated survival has not yet been reported...
  64. ncbi Role of the PDK1-PKB-GSK3 pathway in regulating glycogen synthase and glucose uptake in the heart
    Alfonso Mora
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    FEBS Lett 579:3632-8. 2005
    In order to investigate the importance of the PDK1-PKB-GSK3 signalling network in regulating glycogen synthase (GS) in the heart, we have employed tissue specific conditional knockout mice lacking PDK1 in muscle (mPDK1-/-), as well as ..
  65. ncbi Characterization of phosphatidylinositol 3-kinase-dependent phosphorylation of the hydrophobic motif site Thr(389) in p70 S6 kinase 1
    Angela Romanelli
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    J Biol Chem 277:40281-9. 2002
    ..We report here that co-expression of phosphoinositide-dependent kinase-1 (PDK1) and the phosphatidylinositol 3-kinase-regulated atypical protein kinase Czeta cooperate to increase both ..
  66. pmc Arabidopsis TARGET OF RAPAMYCIN interacts with RAPTOR, which regulates the activity of S6 kinase in response to osmotic stress signals
    Magdy M Mahfouz
    Department of Molecular Genetics and Plant Biotechnology Center, The Ohio State University, Columbus, Ohio 43210, USA
    Plant Cell 18:477-90. 2006
    ..The catalytic domain of S6K1 could be phosphorylated by Arabidopsis 3-phosphoinositide-dependent protein kinase-1 (PDK1), indicating the involvement of PDK1 in the regulation of S6K...
  67. doi Proliferative and antiapoptotic signaling stimulated by nuclear-localized PDK1 results in oncogenesis
    Chintan K Kikani
    Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229, USA
    Sci Signal 5:ra80. 2012
    ..threonine kinase Akt at the cytosolic side of the plasma membrane by phosphoinositide-dependent protein kinase 1 (PDK1), which is recruited and activated by binding to the phosphoinositides produced by PI3K...
  68. doi PDK1 regulates platelet activation and arterial thrombosis
    Xue Chen
    Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai, China
    Blood 121:3718-26. 2013
    The effects of phosphoinositide-dependent protein kinase 1 (PDK1), a master kinase in the phosphoinositide 3-kinase/Akt pathway, on platelet activation are unknown...
  69. doi Crosstalk between PI3 kinase/PDK1/Akt/Rac1 and Ras/Raf/MEK/ERK pathways downstream PDGF receptor
    Emma Tabe Eko Niba
    Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan
    Cell Physiol Biochem 31:905-13. 2013
    Our earlier studies suggested crosstalk between IRS/PI3 kinase/PDK1/Akt/Rac1/ROCK and (Shc2/Grb2/SOS)/Ras/Raf/MEK/ERK pathways downstream PDGF-ββ receptor responsible for chemotaxis and proliferation of malignant mesothelioma cells...
  70. pmc Transition from heterotypic to homotypic PDK1 homodimerization is essential for TCR-mediated NF-κB activation
    Jung Ah Kang
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500 712, Republic of Korea
    J Immunol 190:4508-15. 2013
    Strong NF-κB activation requires ligation of both the CD28 coreceptor and TCR. Phosphoinositide-dependent kinase 1 (PDK1) acts as a scaffold by binding both protein kinase Cθ (PKCθ) and CARMA1, and is therefore essential for signaling ..
  71. doi 2-(3-Oxo-1,3-diphenylpropyl)malonic acids as potent allosteric ligands of the PIF pocket of phosphoinositide-dependent kinase-1: development and prodrug concept
    Adriana Wilhelm
    Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 55:9817-30. 2012
    ..protein kinase C-related kinase 2 (PRK2)-interacting fragment (PIF) pocket of phosphoinositide-dependent kinase-1 (PDK1) was proposed as a novel target site for allosteric modulators...
  72. doi Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer
    Xiaoli Li
    Department of Gerontology, The First Affiliated Hospital, Zhengzhou University, Institute of Clinical Medical Research of Universities in Henan Province, 1 East Jianshe Road, Zhengzhou, Henan Province, People s Republic of China
    Dig Dis Sci 56:2849-56. 2011
    ..Some recent studies show that DNA methylation contributes to down-regulation of microRNA-375 (miR-375) during tumorigenesis. Whether or not down-regulation of miR-375 also exists in esophageal cancer is unknown...
  73. pmc Turning a protein kinase on or off from a single allosteric site via disulfide trapping
    Jack D Sadowsky
    Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California, 1700 Fourth Street, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 108:6056-61. 2011
    ..structurally and functionally how an allosteric site on the Ser/Thr kinase, 3-phosphoinositide-dependent kinase 1 (PDK1)--the PDK1-interacting-fragment (PIF) pocket--is engaged by an activating peptide motif on downstream substrate ..
  74. pmc c-Jun regulates phosphoinositide-dependent kinase 1 transcription: implication for Akt and protein kinase C activities and melanoma tumorigenesis
    Pablo Lopez-Bergami
    Signal Transduction Program, The Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 285:903-13. 2010
    ..Here, we show that c-Jun regulates transcription of phosphoinositide-dependent kinase 1 (PDK1) with a concomitant impact on Akt and protein kinase C (PKC) activity and related substrates...
  75. pmc Allosteric activation of the protein kinase PDK1 with low molecular weight compounds
    Matthias Engel
    Research Group PhosphoSites, Department of Pharmaceutical and Medicinal Chemistry, University of Saarland, Saarbrucken, Germany
    EMBO J 25:5469-80. 2006
    ..the HM/PIF-pocket and have the ability to allosterically activate phosphoinositide-dependent protein kinase 1 (PDK1) by modulating the phosphorylation-dependent conformational transition...
  76. ncbi Dissociation between the translocation and the activation of Akt in fMLP-stimulated human neutrophils--effect of prostaglandin E2
    Chantal Burelout
    Centre de Recherche en Rhumatologie Immunologie, Centre de Recherche du CHUL, 2705 Boul Laurier, Room T1 49, Sainte Foy, Quebec, Canada G1V 4G2
    J Leukoc Biol 81:1523-34. 2007
    ..through phosphorylation on threonine 308 (Thr308) and serine 473 (Ser473) by 3-phosphoinositide-dependent kinase 1 (PDK1) and MAPK-AP kinase (APK)-APK-2 (MAPKAPK-2), respectively, in a PI-3K-dependent manner...
  77. pmc PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer
    S M Wigfield
    Cancer Research UK, Growth Factor Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DU, UK
    Br J Cancer 98:1975-84. 2008
    ..005 split by median). These results indicate that HIF regulation of PDK-1 has a key role in maintaining lactate production in human cancer and that the investigation of PDK-1 inhibitors should be investigated for antitumour effects...
  78. pmc Signal transduction mechanism involved in Clostridium perfringens alpha-toxin-induced superoxide anion generation in rabbit neutrophils
    Masataka Oda
    Faculty of Pharmaceutical Sciences, Department of Microbiology, Tokushima Bunri University, Yamashiro cho, Tokushima 770 8514, Japan
    Infect Immun 74:2876-86. 2006
    ..The toxin induced phosphorylation of 3-phosphoinositide-dependent protein kinase 1 (PDK1)...
  79. ncbi 3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling
    Hiroshi Tanaka
    Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan
    J Biol Chem 280:40965-73. 2005
    ..IkappaB kinase (IKK)/NF-kappaB and phosphatidylinositol 3-OH-kinase/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt pathways regulate various cellular functions, especially cell survival...
  80. ncbi Arabidopsis PDK1: identification of sites important for activity and downstream phosphorylation of S6 kinase
    Lotta Otterhag
    Department of Plant Biochemistry, Lund University, P O Box 124, SE 22100 Lund, Sweden
    Biochimie 88:11-21. 2006
    ..protein kinase AtPDK1 was identified as a homologue of the mammalian 3-phosphoinositide-dependent protein kinase-1 (PDK1), which is involved in a number of physiological processes including cell growth and proliferation...
  81. ncbi The subcellular localization of 3-phosphoinositide-dependent protein kinase is controlled by caveolin-1 binding
    Jaesun Chun
    School of Science Education, Chungbuk National University, Chongju 361 763, Republic of Korea
    Biochem Biophys Res Commun 326:136-46. 2005
    3-Phosphoinositide-dependent protein kinase 1 (PDK1), a member of the serine/threonine kinase family, has been demonstrated to be crucial for cellular survival, differentiation, and metabolism...
  82. pmc Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A
    Likun Li
    Scott Department of Urology, Baylor College of Medicine, 6560 Fannin, Suite 2100, Houston, TX 77030, USA
    Mol Cell Biol 23:9389-404. 2003
    ..Examination of the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling cascade revealed higher activities of PDK1 and Akt but not PI3-K in cav-1-stimulated cells compared to control cells...
  83. ncbi Involvement of Hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1
    Naoya Fujita
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113 0032, Japan
    J Biol Chem 277:10346-53. 2002
    ..upstream Akt kinases, phosphatidylinositide-3-OH kinase (PI3K) and 3-phosphoinositide-dependent protein kinase-1 (PDK1). Hsp90 inhibitors had no effect on PI3K protein expression...
  84. pmc PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia
    Anastasia Mashukova
    Department of Cell Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
    Mol Biol Cell 23:1664-74. 2012
    ..Although there is consensus that phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for newly synthesized molecules, it is unclear what kinase performs that function during ..
  85. pmc Involvement of PDK1, PKC and TOR signalling pathways in basal fluconazole tolerance in Cryptococcus neoformans
    Hyeseung Lee
    Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
    Mol Microbiol 84:130-46. 2012
    This study shows the importance of PDK1, TOR and PKC signalling pathways to the basal tolerance of Cryptococcus neoformans towards fluconazole, the widely used drug for treatment of cryptococcosis...
  86. pmc Acute inhibition of PI3K-PDK1-Akt pathway potentiates insulin secretion through upregulation of newcomer granule fusions in pancreatic β-cells
    Kyota Aoyagi
    Department of Biochemistry, Kyorin University School of Medicine, Tokyo, Japan
    PLoS ONE 7:e47381. 2012
    ..with a series of constitutive active mutants, we showed that the PI3K-3-phosphoinositide dependent kinase-1 (PDK1)-Akt pathway mediated the potentiation of insulin secretion...
  87. pmc Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)
    Rosalia Dettori
    Department of Internal Medicine I, Research Group PhosphoSites, Johann Wolfgang Goethe University Hospital, D 60590 Frankfurt, Germany
    J Biol Chem 284:30318-27. 2009
    ..3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates the activation loop of numerous AGC kinases, including the protein kinase C-related protein kinases ..
  88. ncbi A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta (PKCzeta ) and PKC-related kinase 2 by PDK1
    A Balendran
    MRC Protein Phosphorylation Unit, Division of Signal Transduction Therapy, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 275:20806-13. 2000
    ..The 3-phosphoinositide-dependent protein kinase (PDK1) activates many members of the AGC subfamily of kinases in vitro, including PKCzeta and PRK2 by phosphorylating the ..
  89. pmc Phosphorylation of protein kinase N by phosphoinositide-dependent protein kinase-1 mediates insulin signals to the actin cytoskeleton
    L Q Dong
    Department of Pharmacology and Biochemistry, The University of Texas Health Science Center, San Antonio, TX 78229, USA
    Proc Natl Acad Sci U S A 97:5089-94. 2000
    ..revealed that the phosphatidylinositol 3-kinase downstream effector phosphoinositide-dependent protein kinase-1 (PDK1) interacted with protein kinase N (PKN), a Rho-binding Ser/Thr protein kinase potentially implicated in a variety ..
  90. pmc Functional involvement of protein kinase C-betaII and its substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), in insulin-stimulated glucose transport in L6 rat skeletal muscle cells
    D S Chappell
    Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
    Diabetologia 52:901-11. 2009
    ..phosphorylation cascades, including phosphatidylinositol-3-kinase (PI3K), phosphatidylinositol-dependent kinase (PDK1), Akt, and protein kinase C (PKC)...
  91. pmc Pdk1 activity controls proliferation, survival, and growth of developing pancreatic cells
    Joby J Westmoreland
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Dev Biol 334:285-98. 2009
    ..We generated mice with pancreas-specific ablation of the 3-phosphoinositide-dependent protein kinase 1 (Pdk1) to investigate how signaling downstream of the phosphatidylinositol-3-OH kinase (PI3K) pathway controls pancreas ..
  92. doi Identification of allosteric PIF-pocket ligands for PDK1 using NMR-based fragment screening and 1H-15N TROSY experiments
    Brian J Stockman
    Pfizer Global Research and Development, Groton, CT 06340, USA
    Chem Biol Drug Des 73:179-88. 2009
    ..The binding of substrate in this so-called PDK1 Interacting Fragment pocket allows interaction with 3-phosphoinositide-dependent kinase-1 and enhanced ..
  93. doi New anti-cancer role for PDK1 inhibitors: preventing resistance to tamoxifen
    Christian Peifer
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Biochem J 417:e5-7. 2009
    ..published in this issue of the Biochemical Journal suggests that a signal transduction pathway controlled by PDK1 (phosphoinositide-dependent kinase 1) plays a crucial role in regulating the sensitivity of breast cancer cells to ..
  94. pmc Hypoxia-induced alteration of mitochondrial genes in cardiomyocytes: role of Bnip3 and Pdk1
    Bixi Jian
    Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
    Shock 34:169-75. 2010
    ..upregulated genes after 24 h of hypoxia included hypoxia-inducible factor 1, alpha subunit, inducible genes Bnip3, Pdk1, and Aldoc...
  95. pmc The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB
    R M Biondi
    Division of Signal Transduction Therapy, MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 20:4380-90. 2001
    ..Activation entails phosphorylation of these kinases at two residues, the T-loop and the hydrophobic motif. PDK1 activates S6K, SGK and PKB isoforms by phosphorylating these kinases at their T-loop...
  96. 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
    The pyruvate dehydrogenase complex (PDC) has a pivotal role in islet metabolism. The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of PDC...
  97. pmc AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC
    M P Sajan
    Research Service, James A Haley Veterans Hospital and Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida 33612, USA
    Am J Physiol Endocrinol Metab 298:E179-92. 2010
    ..required for activation of aPKC and ERK; aPKC activation involved and required phosphoinositide-dependent kinase 1 (PDK1) phosphorylation of Thr410-PKC-zeta; aPKC Thr410 phosphorylation and activation also required MEK1-dependent ERK; ..
  98. ncbi Rho GTPase control of protein kinase C-related protein kinase activation by 3-phosphoinositide-dependent protein kinase
    P Flynn
    Imperial Cancer Research Fund, Protein Phosphorylation Laboratory, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 275:11064-70. 2000
    ..in vivo involves the activation loop phosphorylation of PRK1/2 by 3-phosphoinositide-dependent protein kinase-1 (PDK1)...
  99. pmc Reciprocal negative regulation of PDK1 and ASK1 signaling by direct interaction and phosphorylation
    Hyun A Seong
    Department of Biochemistry, Biotechnology Research Institute, School of Life Sciences, Chungbuk National University, Cheongju 361 763, Republic of Korea
    J Biol Chem 285:2397-414. 2010
    ..In this study, we reveal a functional association between PDK1 (3-phosphoinositide-dependent protein kinase 1), a critical mediator of cell survival, and ASK1 (apoptosis signal-..
  100. ncbi 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro
    D R Alessi
    Department of Biochemistry, MRC Phosphorylation Unit, University of Dundee, Dundee, UK
    Curr Biol 8:69-81. 1998
    ..It is not known which protein kinases phosphorylate and activate p70...
  101. doi Novel isoquinolone PDK1 inhibitors discovered through fragment-based lead discovery
    M Catherine Johnson
    Pfizer Global Research and Development, San Diego, CA 92121, USA
    J Comput Aided Mol Des 25:689-98. 2011
    Phosphoinositide-dependent kinase-1 (PDK1) is a critical enzyme in the PI3K/AKT pathway and to the activation of AGC family protein kinases, including S6K, SGK, and PKC...

Research Grants64

  1. PPAR-delta in obesity-related vascular remodeling
    Yuqing Chen; Fiscal Year: 2004
    ..Define the essential role of the PPARdleta-ILK/PDK1-Akt pathway in the regulation of VSMC apoptosis in cell culture models; 3)...
  2. Insulin Signaling in a Cell-Free System
    Michael Mueckler; Fiscal Year: 2007
    ..The threonine phoshorylation is catalyzed by PDK1, a well-characterized serine/threonine kinase, however, the serine kinase has not yet been identified...
  3. Human Skeletal Muscle Proteome and Phosphoproteome in Obesity and Type 2 Diabetes
    ZhengPing Yi; Fiscal Year: 2010
    ..developed in our laboratory to target proteins of interest in the PI-3 kinase pathway, such as PI-3 kinase, PDK1, AKT and AS160...
  4. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2010
    ..We hypothesize that insulin suppresses autophagy by activating insulin and IGF-1 receptors, which act via PI3K-PDK1 and Akt1 and 2 to activate mTOR dependent and independent pathways that suppress autophagy...
  5. Protein Kinase - Primary Structure and cAMP Interaction
    Susan S Taylor; Fiscal Year: 2011
    ..how the catalytic subunit is recognized and phosphorylated on its Activation Loop by an activating kinase, PDK1. In Specific Aim III we address the role of the N-terminal tail and especially the isoform-specific myristylation ..
  6. Protein Kinase - Primary Structure and cAMP Interaction
    Susan S Taylor; Fiscal Year: 2010
    ..how the catalytic subunit is recognized and phosphorylated on its Activation Loop by an activating kinase, PDK1. In Specific Aim III we address the role of the N-terminal tail and especially the isoform-specific myristylation ..
  7. Hepatitis C: E2 Molecular Mechanisms
    Martina Buck; Fiscal Year: 2010
    ..that E2, in the absence of extracellular growth factors, increases the expression and activities of PIP2, PI3K, PDK1 and Akt. This signaling cascade promotes proliferation...
  8. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2009
    ..pathways by assessing the ObRb-JAK2-STAT3/SOCS3-SHP2-PTP1B and the IRbeta tyrosine kinase-IRS1/2-P-l-3-kinase- PDK1/2-Akt1/2/PKC;-PDE38-cAMP pathways and b) the orexigenic (NPY/AgRP) and anorexigenic (alpha-MSH) neuropeptides. II...
  9. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin Devaskar; Fiscal Year: 2009
    ..pathways by assessing the ObRb-JAK2-STAT3/SOCS3-SHP2-PTP1B and the IRbeta tyrosine kinase-IRS1/2-P-l-3-kinase- PDK1/2-Akt1/2/PKC;-PDE38-cAMP pathways and b) the orexigenic (NPY/AgRP) and anorexigenic (alpha-MSH) neuropeptides. II...
  10. Membrane Rafts and Sertoli-Germ Cell Interactions
    SALLY NYQUIST; Fiscal Year: 2002
    ..is phosphatidylinositol 3-kinase (PI3K), as well as downstream enzymes such as phosphoinositide-dependent kinase (PDK1), protein kinase B (PKB), protein kinase C (PKC) and phospholipase C (PLC)...
  11. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin U Devaskar; Fiscal Year: 2010
    ..pathways by assessing the ObRb-JAK2-STAT3/SOCS3-SHP2-PTP1B and the IRbeta tyrosine kinase-IRS1/2-P-l-3-kinase- PDK1/2-Akt1/2/PKC;-PDE38-cAMP pathways and b) the orexigenic (NPY/AgRP) and anorexigenic (alpha-MSH) neuropeptides. II...
  12. PDK1 and PPARdelta Signaling in Mammary Tumorigenesis
    Robert I Glazer; Fiscal Year: 2010
    This proposal will test the hypothesis that 3-phosph6inbsitide-dependent protein kinase-1 (PDK1) activates and interacts with the ff-eaten in/TCF-target gene, peroxisome proliferator-activated receptor-delta (PPARtf)...
  13. PDK1 and PPARdelta Signaling in Mammary Tumorigenesis
    Robert Glazer; Fiscal Year: 2009
    This proposal will test the hypothesis that 3-phosph6inbsitide-dependent protein kinase-1 (PDK1) activates and interacts with the ff-eaten in/TCF-target gene, peroxisome proliferator-activated receptor-delta (PPARtf)...
  14. Pathways that integrate cell growth with the cell cycle
    Douglas R Kellogg; Fiscal Year: 2010
    ..We further found that Rts1 is regulated by the yeast equivalent of the vertebrate PDK1/Akt signaling pathway, which plays conserved roles in the control of cell growth and entry into the cell cycle...
  15. Vascular Oxidases in Migration
    Kathy Griendling; Fiscal Year: 2009
    ..reactive oxygen species (ROS), which mediate the tyrosine phosphorylation of phosphoinositide-dependent kinase-1 (PDK1), a serine/threonine kinase that mediates actin cytoskeletal reorganization...
  16. Vascular Oxidases in Migration
    Kathy Griendling; Fiscal Year: 2007
    ..reactive oxygen species (ROS), which mediate the tyrosine phosphorylation of phosphoinositide-dependent kinase-1 (PDK1), a serine/threonine kinase that mediates actin cytoskeletal reorganization...
  17. PDK1 and PPAR-delta Signaling in Mammary Tumorigenesis
    Robert Glazer; Fiscal Year: 2007
    This proposal will test the hypothesis that 3-phosphoinositide-dependent protein kinase-1 (PDK1) activates and interacts with the ¿-catenin/TCF-target gene, peroxisome proliferator-activated receptor-delta (PPARd) to promote mammary ..
  18. Reactive Oxygen Species Regulation of Vascular Smooth Muscle Cell Migration
    David S Weber; Fiscal Year: 2010
    ..smooth muscle cell migration that are regulated by ROS and have identified 3-phosphoinositide-dependent kinase-1 (PDK1) as a key regulator...
  19. GAB2 in metastatic melanoma
    JULIDE CELEBI; Fiscal Year: 2009
    ..GAB2 mediated hyperactivation of PI3/PDK1/AKT signaling in the absence of growth factors, and inhibition of the PI3K-AKT pathway decreased GAB2-mediated ..
  20. Genetic Markers of GIK Effect in Acute Coronary Syndrome in the IMMEDIATE Trial
    Inga Peter; Fiscal Year: 2007
    ..hypothesize that variations in genes encoding common pathways related to glucose transport and oxidation (GLUT4 and PDK1), insulin signaling and degradation (IRS1 and IDE), fatty acid metabolism regulation (PRKAA2, PPARA, and PPARG), ..
  21. GAB2 in metastatic melanoma
    Julide T Celebi; Fiscal Year: 2010
    ..GAB2 mediated hyperactivation of PI3/PDK1/AKT signaling in the absence of growth factors, and inhibition of the PI3K-AKT pathway decreased GAB2-mediated ..
  22. Genetic Markers of GIK Effect in Acute Coronary Syndrome in the IMMEDIATE Trial
    Inga Peter; Fiscal Year: 2009
    ..hypothesize that variations in genes encoding common pathways related to glucose transport and oxidation (GLUT4 and PDK1), insulin signaling and degradation (IRS1 and IDE), fatty acid metabolism regulation (PRKAA2, PPARA, and PPARG), ..
  23. Erythropoietin Signaling Pathways to c-myc and c-fos
    Changmin Chen; Fiscal Year: 2004
    ..We also hypothesize that the phospholipase C-y (PLCy)/phosphoinositide-dependent protein kinase 1 (PDK1) /PKC-e/unidentified kinase/ MAP kinase kinase (MEK)/MAP kinase (ERK) cascade is involved in the elongation of c-..
  24. PHOSPHOPEPTIDE METABOLISM IN ADIPOCYTES
    Joseph Avruch; Fiscal Year: 2007
    ..This enzyme, called PDK1 is also one of the activators of the cAkt/PKBkinase...
  25. 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...
  26. Function of ATF2 URE binding protein in human melanoma
    ZE apos EV A RONAI; Fiscal Year: 2010
    ..Our preliminary results reveal that c-Jun and Stat3 regulate the transcription of RACK1, PDK1 (the upstream kinase for PKC), suggesting a feed-forward loop mechanism...
  27. Function of ATF2 URE binding protein in human melanoma
    ZE EV RONAI; Fiscal Year: 2007
    ..Our preliminary results reveal that c-Jun and Stat3 regulate the transcription of RACK1, PDK1 (the upstream kinase for PKC), suggesting a feed-forward loop mechanism...
  28. Human Skeletal Muscle Proteome and Phosphoproteome in Obesity and Type 2 Diabetes
    ZhengPing Yi; Fiscal Year: 2010
    ..developed in our laboratory to target proteins of interest in the PI-3 kinase pathway, such as PI-3 kinase, PDK1, AKT and AS160...
  29. 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...
  30. 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...