Genomes and Genes
Gene Symbol: PDK1
Description: pyruvate dehydrogenase kinase 1
Alias: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial, pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial, PDH kinase 1, mitochondrial pyruvate dehydrogenase, lipoamide, kinase isoenzyme 1, pyruvate dehydrogenase kinase, isoenzyme 1
Publications291 found, 100 shown here
- Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERKS 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...
- Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1Jung 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....
- 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 alphaK 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)...
- Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosisAnne 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...
- Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the master growth factor signaling kinase PDK1Iris Z Uras
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
PLoS ONE 7:e31003. 2012Phosphorylation by the phospho-inositide-dependent kinase 1 (PDK1) is essential for many growth factor-activated kinases and thus plays a critical role in various processes such as cell proliferation and metabolism...
- 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1C 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...
- Regulation of kinase activity of 3-phosphoinositide-dependent protein kinase-1 by binding to 14-3-3Saori Sato
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan
J Biol Chem 277:39360-7. 20023-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a central role in activating the protein kinase A, G, and C subfamily...
- PDK1 mediates growth factor-induced Ral-GEF activation by a kinase-independent mechanismXuejun Tian
Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, USA
EMBO J 21:1327-38. 2002..Here we show that Ral-GEF stimulation by EGF involves an additional mechanism, PI3-K-dependent kinase 1 (PDK1)-induced enhancement of Ral-GEF catalytic activity...
- Raptor, a binding partner of target of rapamycin (TOR), mediates TOR actionKenta Hara
Biosignal Research Center, Kobe University, 657 8501, Kobe, Japan
Cell 110:177-89. 2002..elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR. Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo...
- 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....
- HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxiaJung 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...
- PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoESophie Pinner
Tumour Cell Biology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
Nat Cell Biol 10:127-37. 2008..In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo...
- 3-phosphoinositide-dependent protein kinase-1 regulates proliferation and survival of cancer cells with an activated mitogen-activated protein kinase pathwayZhuomei Lu
Schering Plough Research Institute, Kenilworth, NJ 07033, USA
Mol Cancer Res 8:421-32. 2010..This second messenger leads to the recruitment of 3-phosphoinositide-dependent protein kinase-1 (PDK1) to the proximal side of the plasma membrane, which results in the activation of AKT kinase...
- Physical association of PDK1 with AKT1 is sufficient for pathway activation independent of membrane localization and phosphatidylinositol 3 kinaseZhiyong Ding
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
PLoS ONE 5:e9910. 2010..phosphate-mediated recruitment of AKT and its upstream kinases, including 3-Phosphoinositide-dependent kinase 1 (PDK1), to the inner surface of the cell membrane...
- PDK1 recruitment to the SHPS-1 signaling complex enhances insulin-like growth factor-i-stimulated AKT activation and vascular smooth muscle cell survivalXinchun Shen
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
J Biol Chem 285:29416-24. 2010..Therefore, we investigated the mechanism of PDK1 recruitment to the SHPS-1 signaling complex and the consequences of disrupting PDK1 recruitment for downstream ..
- 3-phosphoinositide-dependent kinase 1 controls breast tumor growth in a kinase-dependent but Akt-independent mannerPaolo Armando Gagliardi
Institute for Cancer Research and Treatment, Candiolo, Italy
Neoplasia 14:719-31. 20123-phosphoinositide-dependent protein kinase 1 (PDK1) is the pivotal element of the phosphatidylinositol 3 kinase (PI3K) signaling pathway because it phosphorylates Akt/PKB through interactions with phosphatidylinositol 3,4,5 phosphate...
- Sphingosine is a novel activator of 3-phosphoinositide-dependent kinase 1C 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. 20003-Phosphoinositide-dependent kinase 1 (PDK1) has previously been shown to phosphorylate the activation loop of several AGC kinase family members...
- Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1Ayaz Najafov
University of Dundee, Scotland, UK
Biochem J 433:357-69. 2011b>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 ..
- Evidence that 3-phosphoinositide-dependent protein kinase-1 mediates phosphorylation of p70 S6 kinase in vivo at Thr-412 as well as Thr-252A 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...
- 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...
- Characterization of PDK2 activity against protein kinase B gammaConrad 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, ..
- Mechanism of PDK1-catalyzed Thr-229 phosphorylation of the S6K1 protein kinaseMalik M Keshwani
Department of Chemistry, University of Miami, Coral Gables, Florida 33124, USA
J Biol Chem 284:22611-24. 2009b>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-..
- 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)...
- 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 PDK2T 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...
- 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinaseD 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-..
- 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...
- Regulation of protein kinase Mzeta synthesis by multiple kinases in long-term potentiationMatthew 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...
- 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 cellsLuciano 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 ..
- PDK1 and PKB/Akt: ideal targets for development of new strategies to structure-based drug designThomas 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)...
- Fluorescence resonance energy transfer in quantum dot-protein kinase assembliesIbrahim 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...
- Reduced Ca2+ entry and suicidal death of erythrocytes in PDK1 hypomorphic miceMichael Foller
Department of Physiology, University of Tuebingen, Gmelinstr 5, 72076 Tubingen, Germany
Pflugers Arch 455:939-49. 2008The 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...
- Phase I trial of UCN-01 in combination with topotecan in patients with advanced solid cancers: a Princess Margaret Hospital Phase II Consortium studyS 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 ..
- The survival pathways phosphatidylinositol-3 kinase (PI3-K)/phosphoinositide-dependent protein kinase 1 (PDK1)/Akt modulate liver regeneration through hepatocyte size rather than proliferationSanae 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-..
- Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinaseT 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...
- Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidationM 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. 2000The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC)...
- Role of PDK1 in regulation of gastric acid secretionAnand 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...
- Sphingoid base signaling via Pkh kinases is required for endocytosis in yeastS 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...
- Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migrationDavid 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 ..
- Identification of calcium-regulated heat-stable protein of 24 kDa (CRHSP24) as a physiological substrate for PKB and RSK using KESTRELGillian 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 ..
- Identification of tyrosine phosphorylation sites on 3-phosphoinositide-dependent protein kinase-1 and their role in regulating kinase activityJ Park
Friedrich Miescher Institute, Maulbeerstrasse 66, Basel CH 4058, Switzerland
J Biol Chem 276:37459-71. 20013-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a central role in signal transduction pathways that activate phosphoinositide 3-kinase...
- Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failureAlfonso 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. 2005The 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 ..
- Regulation of gastric acid secretion by PKB/Akt2Anand 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...
- Receptor association and tyrosine phosphorylation of S6 kinasesHeike 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...
- Leflunomide inhibits PDK1/Akt pathway and induces apoptosis of human mast cellsNorifumi 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...
- Potential inhibition of PDK1/Akt signaling by phenothiazines suppresses cancer cell proliferation and survivalJang 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. 20083'-Phosphoinositide-dependent kinase-1 (PDK1) has been identified for its ability to phosphorylate and activate Akt...
- PDK1 and HR46 gene homologs tie social behavior to ovary signalsYing 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 ..
- Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cellsEmily 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 ..
- 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. 2006Pyruvate dehydrogenase kinase isoforms (PDK1-4) are the molecular switch that down-regulates activity of the human pyruvate dehydrogenase complex through reversible phosphorylation...
- Reciprocal control of pyruvate dehydrogenase kinase and phosphatase by inositol phosphoglycans. Dynamic state set by "push-pull" systemPatricia 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)...
- 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 deathA 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)...
- Role of PDK1 in insulin-signaling pathway for glucose metabolism in 3T3-L1 adipocytesTetsuya 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. 2002To 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 ..
- 3-phosphoinositide-dependent protein kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinasesZhihui 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 ..
- Combined 3D-QSAR modeling and molecular docking study on indolinone derivatives as inhibitors of 3-phosphoinositide-dependent protein kinase-1Mohamed 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. 20083-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for developing novel anticancer drugs...
- 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinomaMatthew 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...
- Activation of the cardiac mTOR/p70(S6K) pathway by leucine requires PDK1 and correlates with PRAS40 phosphorylationCossette 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)...
- Chemotactic activation of Dictyostelium AGC-family kinases AKT and PKBR1 requires separate but coordinated functions of PDK1 and TORC2Xin 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...
- Characterization of phosphatidylinositol 3-kinase-dependent phosphorylation of the hydrophobic motif site Thr(389) in p70 S6 kinase 1Angela 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 ..
- Role of the PDK1-PKB-GSK3 pathway in regulating glycogen synthase and glucose uptake in the heartAlfonso 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. 2005In 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 ..
- Impaired intestinal NHE3 activity in the PDK1 hypomorphic mouseCiprian 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...
- The Arabidopsis protein kinase PTI1-2 is activated by convergent phosphatidic acid and oxidative stress signaling pathways downstream of PDK1 and OXI1Richard 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. 2006Arabidopsis 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...
- Pdk1 kinase regulates basal disease resistance through the OsOxi1-OsPti1a phosphorylation cascade in riceHidenori 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)...
- Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinaseX Wang
Division of Molecular Physiology and MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee DD1 5EH, UK
EMBO J 20:4370-9. 2001..of eEF2 phosphorylation and eEF2k activity is lost in cells in which phosphoinositide-dependent kinase 1 (PDK1) has been genetically knocked out...
- 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)...
- Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1David Komander
Division of Biological Chemistry and Molecular Microbiology, University of Dundee, Dundee DD1 5EH, Scotland
Structure 12:215-26. 2004..analysis with a panel of 29 protein kinases reveals that these bisindolyl maleimide inhibitors also inhibit PDK1, a key kinase from the insulin signaling pathway, albeit in the lower microM range...
- Role of the p70(S6K) pathway in regulating the actin cytoskeleton and cell migrationLeise A Berven
Molecular Signalling Group, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australia
Exp Cell Res 296:183-95. 2004..Immunocytochemical studies showed that p70(S6K), Akt1, PDK1, and p85 phosphoinositide 3-kinase (PI 3-kinase) were localized to the actin arc, a caveolin-enriched cytoskeletal ..
- Differential roles of PDK1- and PDK2-phosphorylation sites in the yeast AGC kinases Ypk1, Pkc1 and Sch9Françoise M Roelants
Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720 3202, USA
Microbiology 150:3289-304. 2004Saccharomyces cerevisiae Pkh1 and Pkh2 (orthologues of mammalian protein kinase, PDK1) are functionally redundant...
- In vivo role of the phosphate groove of PDK1 defined by knockin mutationBarry 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)...
- Phosphoinositide-dependent kinase l (PDK1) haplo-insufficiency inhibits production of alpha/beta (alpha/beta) but not gamma delta (gamma/delta) T lymphocytesApril P Kelly
Division of Cell Biology and Immunology, School of Life Sciences, WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
FEBS Lett 580:2135-40. 2006In the present study, we have explored the impact of deleting a single allele of PDK1 in T cell progenitors on alpha/beta and gamma/delta T cell development...
- 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 (1.9-fold), and PDK4 (3.1-fold). High glucose increased PDK1 (1.8-fold) and PDK2 (2...
- Phosphorylation of TNF-alpha converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activationQing Zhang
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Proc Natl Acad Sci U S A 103:6901-6. 2006..Phosphoinositide-dependent kinase 1 (PDK1), a downstream target of PI3-K, has been identified as the previously undescribed kinase to directly phosphorylate ..
- Role of the Phox homology domain and phosphorylation in activation of serum and glucocorticoid-regulated kinase-3Maude Tessier
Samuel Lunenfeld Research Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X5, Canada
J Biol Chem 281:23978-89. 2006..b>PDK1 phosphorylates endosome-associated SGK3 at Thr-320, whereas diversion of SGK3 to the plasma membrane, where PDK1 ..
- 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..dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4)...
- Reconstitution of modular PDK1 functions on trans-splicing of the regulatory PH and catalytic kinase domainsHassan 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. 2007The 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 ..
- Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cellsEllen 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...
- The kinase PDK1 integrates T cell antigen receptor and CD28 coreceptor signaling to induce NF-kappaB and activate T cellsSung Gyoo Park
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Nat Immunol 10:158-66. 2009..We show here that phosphoinositide-dependent kinase 1 (PDK1) is essential for integrating the TCR and CD28 signals...
- Revealing signaling in single cells by single- and two-photon fluorescence lifetime imaging microscopyDamien Alcor
Cell Biophysics Laboratory, Cancer Research UK, London, UK
Methods Mol Biol 462:307-43. 2009..as (1) spatio-temporal interaction of protein kinase B (PKB) with 3-phosphoinositide dependent protein kinase-1 (PDK1), (2) PKB conformation change, (3) dynamics of PKB activation, (4) interaction of phosphatidylinositol transfer ..
- Activation of the PI3K/Akt pathway early during vaccinia and cowpox virus infections is required for both host survival and viral replicationJamária 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...
- TOB suppresses breast cancer tumorigenesisSEAN O'MALLEY
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW, Washington, DC, USA
Int J Cancer 125:1805-13. 2009..Furthermore, decreased activity of Erk2, AKT, CrkL, PDK1, and Smads were observed in TOB-overexpressing cells...
- Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domainsBenchun Miao
Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, USA
Proc Natl Acad Sci U S A 107:20126-31. 2010..PITs inhibit interactions of a number of PIP3-binding PH domains, including those of Akt and PDK1, without affecting several PIP2-selective PH domains...
- Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gainAnutosh Chakraborty
The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Cell 143:897-910. 2010..IP7 affects this pathway by potently inhibiting the PDK1 phosphorylation of Akt, preventing its activation and thereby affecting insulin signaling...
- Developmental expression changes of the genes involved in IGFI signaling pathway in longissimus dorsi muscle of Tongcheng and Yorkshire pigs during postnatal growthQingzhen Jiao
Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, Wuhan, People s Republic of China
Mol Biol Rep 38:5133-8. 2011..contribute to increased DNA content in postnatal myofibre hypertrophy via GRB2-Ras-Raf-MEK-ERK sub-pathway; INSR, PDK1, IRS1 and eIF4E may contribute to high growth rate via stimulating the rate of protein synthesis and inhibiting the ..
- Thymosin-β4 (Tβ4) blunts PDGF-dependent phosphorylation and binding of AKT to actin in hepatic stellate cellsKarina Reyes-Gordillo
Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC, USA
Am J Pathol 178:2100-8. 2011..phosphorylation, the activation of phosphoinositide 3-kinase (PI3K), pyruvate dehydrogenase kinase isozyme 1 (PDK1), and mammalian target of rapamycin (mTOR)...
- Yeast 3-phosphoinositide-dependent protein kinase-1 (PDK1) orthologs Pkh1-3 differentially regulate phosphorylation of protein kinase A (PKA) and the protein kinase B (PKB)/S6K ortholog Sch9Karin Voordeckers
Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, Katholieke Universiteit Leuven and Department of Molecular Microbiology, VIB, B 3001 Leuven Heverlee, Flanders, Belgium
J Biol Chem 286:22017-27. 2011Pkh1, -2, and -3 are the yeast orthologs of mammalian 3-phosphoinositide-dependent protein kinase-1 (PDK1). Although essential for viability, their functioning remains poorly understood...
- Hydroxytyrosol induces vascular smooth muscle cells apoptosis through NO production and PP2A activation with subsequent inactivation of AktHouda Zrelli
Graduate School of Life and Environment Sciences, Alliance for Research on North Africa, University of Tsukuba, Ibaraki, Japan
Planta Med 77:1680-6. 2011..In contrast, the phosphorylation of phosphoinositide-dependent protein kinase 1 (PDK1), an upstream activator of Akt, was not affected by HT...
- Changes in HIF-1α protein, pyruvate dehydrogenase phosphorylation, and activity with exercise in acute and chronic hypoxiaChristophe M R Le Moine
Department of Biology, McMaster University, Hamilton, Ontario, Canada
Am J Physiol Regul Integr Comp Physiol 301:R1098-104. 2011..with a higher phosphorylation (inactive) state of the Ser(232) residue of PDH, a site specific to PDH kinase-1 (PDK1)...
- S6K inhibition renders cardiac protection against myocardial infarction through PDK1 phosphorylation of AktRuomin Di
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China
Biochem J 441:199-207. 2012..Cardiomyocyte-specific deletion of PDK1 (phosphoinositide-dependent kinase 1) and Akt1/3 abolished cardioprotection after MI in the presence of rapamycin ..
- The signaling mechanisms mediating the inhibitory effect of TCH-1116 on formyl peptide-stimulated superoxide anion generation in neutrophilsYa Ru Tsai
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan, ROC
Eur J Pharmacol 682:171-80. 2012..recombinant PDK (3-phosphoinositide-dependent kinase) 1, whereas it had no effect on recruitment of Akt, phospho-PDK1 (Ser241) and p110γ to membrane...
- Advancing age is associated with gene expression changes resembling mTOR inhibition: evidence from two human populationsLorna W Harries
Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX2 5DW, UK
Mech Ageing Dev 133:556-62. 2012..8 genes were robustly associated with age in both cohorts. Genes involved in insulin signaling (PTEN, PI3K, PDK1), ribosomal biogenesis (S6K), lipid metabolism (SREBF1), cellular apoptosis (SGK1), angiogenesis (VEGFB), insulin ..
- Targeting 3-phosphoinoside-dependent kinase-1 to inhibit insulin-like growth factor-I induced AKT and p70 S6 kinase activation in breast cancer cellsSangita M Baxi
Oncology Research, Pfizer Worldwide Research and Development, San Diego, California, United States of America
PLoS ONE 7:e48402. 2012..which in turn recruits and activates proteins that contain a pleckstrin homology (PH) domain, including AKT and PDK1. PDK1 is highly expressed in breast tumor samples and breast cancer cell lines...
- 2-Deoxyglucose treatment complements the cisplatin- or BH3-only mimetic-induced suppression of neuroblastoma cell growthJiin Haur Chuang
The Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Int J Biochem Cell Biol 45:944-51. 2013..Further analysis showed that 2DG decreased both PDK1 and the ATP content. [corrected]...
- Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathwayWen Ying Chuang
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
Thromb Haemost 109:1120-30. 2013..In addition, sulforaphane caused ubiquitination and degradation of phosphoinositide-dependent kinase 1 (PDK1), which is required for Akt activation...
- PTPN12 promotes resistance to oxidative stress and supports tumorigenesis by regulating FOXO signalingI S Harris
1 The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada 2 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Oncogene 33:1047-54. 2014..PTPN12-mediated regulation of ROS appeared to be mediated by phosphoinositide-dependent kinase-1 (PDK1), which was hyperstimulated in the absence of PTPN12...
- Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspringLisa M Nicholas
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
FASEB J 27:3786-96. 2013..05), PDK1 (P<0.01), phospho-PDK1 (P<0.05), and aPKCζ (P<0.05) and in decreased PEPCK-C (P<0...
- Crystal structures of S6K1 provide insights into the regulation mechanism of S6K1 by the hydrophobic motifJianchuan Wang
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
Biochem J 454:39-47. 2013..motif by mTORC1 (mammalian target of rapamycin complex 1) and phosphorylation of Thr229 in the activation loop by PDK1 (phosphoinositide-dependent kinase 1); however, the order of the two events is still ambiguous...
- Compared analysis of LncRNA expression profiling in pdk1 gene knockout mice at two time pointsHailang Liu
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P R China
Cell Physiol Biochem 32:1497-508. 2013..However, studies of LncRNA in heart failure have not yet been reported. Here, we investigated cardiac lncRNA expression profiles in the myocardial-specific knockout pdk1 gene (KO) mouse model of heart failure.
- Modulation of hypoxia-signaling pathways by extracellular linc-RoRKenji Takahashi
Mayo Clinic, Jacksonville, FL 32224, USA
J Cell Sci 127:1585-94. 2014..Compared with controls, siRNA to linc-RoR decreased phosphorylation of p70S6K1 (RPS6KB1), PDK1 and HIF-1α protein expression and increased expression of the linc-RoR target microRNA-145 (miR-145)...
- GABARBP down-regulates HIF-1α expression through the VEGFR-2 and PI3K/mTOR/4E-BP1 pathwaysSung Ho Park
Department of Obstetrics and Gynecology, Hallym University, 948 1, Daerim 1 dong, Yeongdeungpo gu, Seoul 150 950, Republic of Korea
Cell Signal 26:1506-13. 2014..mechanism, GABARBP was found to effectively inhibit the phosphorylation of down-stream PI3K components, such as PDK1, Akt, mTOR, TSC-2, p70S6K, and 4E-BP1 by directly binding with VEGFR-2...
- Justicidin A-induced autophagy flux enhances apoptosis of human colorectal cancer cells via class III PI3K and Atg5 pathwayShen Jeu Won
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
J Cell Physiol 230:930-46. 2015..In addition, the expression of autophagy signaling pathway-related molecules p-PDK1, p-mTOR, p-p70S6k/p-RPS6KB2 was decreased, whereas that of class III PI3K, Beclin 1, Atg5-Atg12, and mitochondrial ..
- Threonine 34 phosphorylation by phosphoinositide-dependent protein kinase 1 facilitates dissociation of Akt from the plasma membraneBill X Huang
Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892 9410, United States
Int J Biochem Cell Biol 64:195-201. 2015..report, we demonstrate that membrane dissociation of Akt requires phosphoinositide-dependent protein kinase 1 (PDK1) which directly phosphorylates not only T308 but also T34 in the pleckstrin homology (PH) domain...
- Breast cancer carcinoma-associated fibroblasts differ from breast fibroblasts in immunological and extracellular matrix regulating pathwaysI Pasanen
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu MRC Oulu, University of Oulu and Oulu University Hospital, P O Box 5000, Oulu FIN 90014, Finland Department of Anatomy and Cell Biology, Oulu University Hospital, Finland Electronic address
Exp Cell Res 344:53-66. 2016..001). Under hypoxic conditions, the expression levels of pyruvate dehydrogenase kinase-1 (PDK1) and pyruvate dehydrogenase kinase-4 (PDK4) were lower in CAFs when compared to NFs (fold changes 0.6 and 0...
- Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancerYujun Hao
Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Nat Commun 7:11971. 2016..Mutant p110α upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis...
- Insulin Signaling and the Heart in DiabetesEVAN DALE ABEL; Fiscal Year: 2011..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...
- ZhengPing Yi; Fiscal Year: 2016..developed in our laboratory to target proteins of interest in the PI-3 kinase pathway, such as PI-3 kinase, PDK1, AKT and AS160...
- HEPATOCELLULAR CARCINOMA AND HEPATITIS C: E2 MOLECULAR MECHANISMSMartina Buck; Fiscal Year: 2010..studies, we have also found that E2, in the absence of extracellular growth factors, increases PIP2, PI3K, PDK1 and Akt, as well as their activities. This signaling cascade promotes proliferation...
- TERRY JUSTIN RETTENMAIER; Fiscal Year: 2015..This proposal focuses on the protein kinase PDK1 where this allosteric site, known as the PIF pocket, is required for the phosphorylation of most PDK1 substrates...
- Characterization of the Sch9 -Longevity Pathway in YeastRobert C Dickson; Fiscal Year: 2013..sphingolipid long chain bases (LCBs) and Pkh1, a homolog of human phosphoinositide-dependent protein kinase 1 (PDK1), as the first upstream regulator of Sch9...
- Wei Dai; Fiscal Year: 2015..The major signaling axis mediated by PI3K, PDK1, and Akt (also referred as protein kinase B) plays a significant role in the regulation of HIF-11 expression...
- Martina Buck; Fiscal Year: 2014..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...
- Protein Kinase - Primary Structure and cAMP InteractionSusan S Taylor; Fiscal Year: 2013..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 ..
- 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...
- The kinase toolbox: Mapping the spatial and temporal regulation of cell signalingSivaraj Sivaramakrishnan; Fiscal Year: 2013..the similarities and differences in the regulation of five closely related AGC kinases (PKA, Akt/PKB, PKC, PDK1 and S6K1)...
- PKC Isoenzymes and Diabetic Microvascular HyperpermeabilitySarah Y Yuan; Fiscal Year: 2010..diabetes upregulates PKCbeta in microvascular endothelium at multiple levels via MAPK-stimulated gene expression, PDK1-potentiated catalytic activity, and DAG-mediated kinase activation...
- Preclinical testing of a novel PDK1 inhibitor for treating vestibular schwannomaAbraham Jacob; Fiscal Year: 2013..The research focus of my proposal is the preclinical development of OSU-03012, a novel PDK1 inhibitor that targets AKT signaling in vestibular schwannomas (VS)...
- Visualizing changes in tumor metabolism using fuctional PET imagingNicholas C Denko; Fiscal Year: 2012..Our recent work has identified the hypoxia-inducible gene pyruvate dehydroggenase kinase 1 (PDK1) as one factor that contributes to this metabolic shift by downregulating mitochondrial function...
- Satya P Kunapuli; Fiscal Year: 2016..In this application, we propose to test the overall hypothesis that PDK1-Akt-Pyk2 axis regulates platelet functional responses...
- Reactive Oxygen Species Regulation of Vascular Smooth Muscle Cell MigrationDavid S Weber; Fiscal Year: 2012..smooth muscle cell migration that are regulated by ROS and have identified 3-phosphoinositide-dependent kinase-1 (PDK1) as a key regulator...
- PERINATAL METABOLIC AND HORMONAL EFFECTSSherin 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...
- Genetic Markers of GIK Effect in Acute Coronary Syndrome in the IMMEDIATE TrialInga Peter; Fiscal Year: 2012..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), ..
- Sankar Ghosh; Fiscal Year: 2016..Recent work in our laboratory has revealed that the protein kinase PDK1 and the transcription factor NF-?B play a critical role in Treg development and function...
- Ze ev A Ronai; Fiscal Year: 2015..attention has been paid to the potential therapeutic importance of 3-phosphoinositide-dependent protein kinase 1 (PDK1), a regulator of the AKT and PKC signaling pathways...
- Zheng Yi Chen; Fiscal Year: 2015..Further, we will specifically block two IGF1 signaling pathways: PI3K/Pdk1/Akt and Raf/Mek/Erk, to assess their respective role in the survival of Rb1-/- cochlear hair cells...
- Shi Long Lu; Fiscal Year: 2015..Preliminary molecular analysis of these tumors suggests that rather than AKT, PDK1 facilitates progression of PI3K-driven HNSCC, and enhanced TGFb signaling may further contribute to this process...
- The Molecular Basis of OX40 on CD4 T CellsMichael Croft; Fiscal Year: 2012..Specifically, we will determine whether OX40 utilizes PKC0, PDK1, and MEK1/ERK to target Akt and NF-KB, and how these signaling cascades impact the expression and function of ..
- Donna L Farber; Fiscal Year: 2014..We developed a novel conditional knockout mouse model in which the phosphoinositide dependent kinase- 1 (PDK1) is specifically ablated in a subset of CD4+ effector/memory T cells and regulatory T cells (Tregs), which are also ..
- Role of Programmed Cell Death10 (PDCD10) in p38 MAP kinase activation and PDK1 siSompop Bencharit; Fiscal Year: 2010..that (1) PDCD10 regulates p38 activation through its interaction with OSM, and (2) PDCD10 participates in PDK1 signaling via its interactions with phospholipids, and PDK1...
- APOPTOSIS IN SUBSTANTIA NIGRARobert E Burke; Fiscal Year: 2011..In the third and final Aim, we will use conditional gene deletion to determine the role of PDK1, a master regulator of the AGC family of kinases in maintaining the viability of dopamine neurons during ..
- Damian J Krysan; Fiscal Year: 2016..Application of this strategy has rapidly led to the identification of human phosphoinositide dependent kinase-1 (PDK1) inhibitors as highly active antifungal molecules in vitro...
- GAB2 in metastatic melanomaJulide T Celebi; Fiscal Year: 2013..GAB2 mediated hyperactivation of PI3/PDK1/AKT signaling in the absence of growth factors, and inhibition of the PI3K-AKT pathway decreased GAB2-mediated ..
- Douglas R Kellogg; Fiscal Year: 2016..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...
- Membrane Rafts and Sertoli-Germ Cell InteractionsSALLY 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)...
- PDK1 and PPARdelta Signaling in Mammary TumorigenesisRobert I Glazer; Fiscal Year: 2010This 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)...
- Erythropoietin Signaling Pathways to c-myc and c-fosChangmin 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-..
- PPAR-delta in obesity-related vascular remodelingYuqing Chen; Fiscal Year: 2007..Define the essential role of the PPARdelta-ILK/PDK1-Akt pathway in the regulation of VSMC apoptosis in cell culture models; 3)...
- MECHANISMS REGULATING AIRWAY MUSCLE GROWTHReynold Panettieri; Fiscal Year: 2003..by Src and activates PtdIns 3-kinase, whereas Protein Kinase B (PKB) and phosphotidylinositol-dependent kinase 1 (PDK1) serve critical roles as both downstream effectors of PtdIns 3-kinase and upstream modulators of p70s6k...
- Phospholipid signaling in B LymphocytesROBERT RICKERT; Fiscal Year: 2009..In particular, PDK1 has been identified as a pivotal downstream effector of PI3K that activates Akt, p70S6kinase, PKC enzymes and other ..
- Cell Transformation by Dbl-like onco-proteinsDanny Manor; Fiscal Year: 2006..Cdc42 that is a likely candidate for mediating Dbl- transformation signals and to characterize the signaling pathway that originates from Dbl and leads to stimulation of survival pathways via activation of PDK1 and Akt.
- MECHANISMS AND ROLES OF PDK1 IN INSULIN SIGNALINGFeng Liu; Fiscal Year: 2003..is focusing on a newly identified serine/threonine kinase, the phosphoinositide-dependent protein kinase 1 (PDK1)...
- ION CHANNEL REGULATION BY THE CYTOPLASMIC TAIL OF PDK1Seth Alper; Fiscal Year: 2005..We will search for novel interacting proteins, and prepare protein suitable for structural analysis. ..
- Probing the mechanisms of signal transduction via adiponectin and its receptorsThomas Lyons; Fiscal Year: 2007..Furthermore, it is proposed that these receptors, via the generation of a sphingosine second messenger, activate PDK1 and downstream AGC kinase pathways known to be involved in glucose sensing (protein kinase A, protein kinase B or ..
- A Phase I Study of the AKT Inhibitor 17-AAG in CLLThomas Lin; Fiscal Year: 2006..Specifically, we will examine the effects of 17-AAG on the PDK1/AKT/TCL-1 pathway and other proteins dependent upon Hsp90 binding...
- Second-Messenger Induced Activation of PDK1 and Protein Kinase BThomas Harris; Fiscal Year: 2008..In addition to a catalytic or kinase domain, PDK1 and PKB also contain a pleckstrin homology (PH) domain, which binds to the second messenger and results in the ..
- S6 Phosphorylation & Tyrosine Protein KinasesJAMES MALLER; Fiscal Year: 2004..Experiments will evaluate whether Bub1 mediates CSF arrest by the MAPK pathway. This work provides a link between the MAPK/Rsk pathway and checkpoint control of the cell cycle at the metaphase/anaphase transition. ..
- Ovarian Follicular Developmental and Hormone ActionJoanne Richards; Fiscal Year: 2007..3) Determine the molecular, cellular and hormonal basis of the altered ovarian phenotype of the TAFII105 null mice. 4) Determine the function of Wnt-4 in the adult ovary. ..
- Chemokines, nitric oxide, and myocardial depressionBysani Chandrasekar; Fiscal Year: 2005..The results from these studies will further our knowledge of chemokine biology and lead to new therapeutic strategies to prevent or treat myocardial dysfunction in ischemia-reperfusion injury. ..
- Effective Mammalian Two Hybrid Screening ApproachZhiyong Ding; Fiscal Year: 2008..Thus the technology will uncover functional protein-protein interactions not detectable by other approaches and advance our understanding of protein functions and signaling networks in cancer. [unreadable] [unreadable] [unreadable]..
- A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANSMARTHA OR MARTY SLATTERY; Fiscal Year: 2006..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
- Hypoxia-Inducible Factor 1 and Oxygen HomeostasisGregg Semenza; Fiscal Year: 2009....
- LH ACTION IN OVARIAN CELL DIFFERENTIATIONJoanne Richards; Fiscal Year: 2007..A related and longer term goal of the research is to identify and characterize the genes regulated by LH, prostaglandins (PGs), and C/EBPs that control key steps in the ovulatory process. ..
- NEONATAL CARDIAC RESPONSE TO MYOFILAMENT DEGENERATIONMark Sussman; Fiscal Year: 2001....
- REGULATION OF MAMMALIAN DIHYDROLIPOAMIDE DEHYDROGENASEMulchand Patel; Fiscal Year: 2002..abstract_text> ..
- EXPRESSION OF HUMAN ERYTHROPOIETIN GENEGregg Semenza; Fiscal Year: 2002..abstract_text> ..
- CONTROL OF CELL DIVISION IN XENOPUS OOCYTESJAMES MALLER; Fiscal Year: 2003..Further work will examine the regulation, localization, and targets of PIx1 and identify kinases that activate xPIkk1. ..
- FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDYMARTHA OR MARTY SLATTERY; Fiscal Year: 2003..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
- CYTOSKELETAL ADHESION IN CARDIAC REMODELINGMark Sussman; Fiscal Year: 2004..Results of this study will identify molecular regulators of dilation and open new potential therapeutic targets for pharmaceutical intervention. ..
- NUCLEOTIDE-MEDIATED LEUKOCYTE STIMULATIONSatya Kunapuli; Fiscal Year: 2004..The studies proposed in this application will also help us understand the mechanisms of neutrophil activation and contribute to the knowledge of better treatments and to the design of therapeutics for inflammatory diseases. ..
- POSTRECEPTOR DYSREGULATION IN DEPRESSIONYogesh Dwivedi; Fiscal Year: 2004..abstract_text> ..
- 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. ..
- Growth Factors and Colon CancerMARTHA OR MARTY SLATTERY; Fiscal Year: 2006..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
- Functional G Protein pathways in platelet activationSatya P Kunapuli; Fiscal Year: 2010..These studies will enhance our understanding of the signaling pathways and their role in platelet activation, and might identify potential newer targets for the treatment of thrombosis. ..
- Role of Hsp27 in regulation of Neutrophil ApoptosisMadhavi Rane; Fiscal Year: 2006..These studies will lead us to new targets for disrupting neutrophil-mediated tissue damage in inflammatory diseases. [unreadable] [unreadable] [unreadable]..
- DIET AND SOMATIC MUTATIONS IN COLON CANCERMARTHA OR MARTY SLATTERY; Fiscal Year: 2007..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
- Signal Transduction Mechanisms in Suicide BrainYogesh Dwivedi; Fiscal Year: 2008..abstract_text> ..
- Platelet ADP receptorsSatya Kunapuli; Fiscal Year: 2008..We further propose to evaluate the relative contribution of the P2Y1 and the P2Y12 receptors to thrombus formation, using P2Y1 or P2Y12 deficient mice and treatment with antagonists and models of in vivo thrombosis and thromboembolism. ..
- Validating microRNA Analysis in Human Postmortem BrainYogesh Dwivedi; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- DIET INDUCED HYPERINSULINEMIA AND BETA CELL FUNCTIONMulchand Patel; Fiscal Year: 2001..This unique rat model has the potential for providing new and significant insight into the "fuel hypothesis" for altered insulin secretory response in response to diet and maternal influences on fetal pancreatic adaptations. ..
- Mechanism and Molecular Recognition in Human Pyruvate Dehydrogenase ComplexMulchand Patel; Fiscal Year: 2008..abstract_text> ..
- Modulation of Neutrophil Apoptosis by Akt-Hsp27 SignalosomeMadhavi Rane; Fiscal Year: 2008..These studies will lead us to new targets for disrupting neutrophil-mediated tissue damage in inflammatory diseases. ..
- LH ACTION IN OVARIAN CELL DIFFERENTIATIONJoanne Richards; Fiscal Year: 2008..Specific Aim II: Determine the function of AREG target genes that are uniquely expressed at high levels in ovulated COCs (compared to granulosa cells) and that impact ovulation. ..