protein kinases

Summary

Summary: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37.

Top Publications

  1. ncbi DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:5858-68. 1998
  2. ncbi Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
    D D Sarbassov
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 307:1098-101. 2005
  3. ncbi Plant stomata function in innate immunity against bacterial invasion
    Maeli Melotto
    Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
    Cell 126:969-80. 2006
  4. ncbi Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
    Alexander Zimprich
    Department of Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tubingen, 72076 Tubingen, Germany
    Neuron 44:601-7. 2004
  5. ncbi The protein kinase complement of the human genome
    G Manning
    SUGEN Inc, 230 East Grand Avenue, South San Francisco, CA 94080, USA
    Science 298:1912-34. 2002
  6. ncbi Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease
    Coro Paisan-Ruiz
    Unitat de Genetica Molecular, Departament de Genòmica i Proteòmica, Institut de Biomedicina de València CSIC, E46010 Valencia, Spain
    Neuron 44:595-600. 2004
  7. pmc A global protein kinase and phosphatase interaction network in yeast
    Ashton Breitkreutz
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada
    Science 328:1043-6. 2010
  8. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
  9. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
  10. ncbi Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
    Ira E Clark
    Nature 441:1162-6. 2006

Research Grants

  1. Xenoestrogen regulation of Leydig cells
    BENSON TOKUNBO AKINGBEMI; Fiscal Year: 2010
  2. Cory Teuscher; Fiscal Year: 2014
  3. Role of Chromogranin A in Metabolic Syndrome
    Sushil K Mahata; Fiscal Year: 2013
  4. VINCENT SCOTT TAGLIABRACCI; Fiscal Year: 2014
  5. Emilio B Gonzalez; Fiscal Year: 2014
  6. CLIFFORD RUSSELL GREYSON; Fiscal Year: 2016
  7. JAMES RUSSELL SOWERS; Fiscal Year: 2015
  8. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
  9. Cellular &Inflammatory Pathways in Ashtma &Allergic Diseases: From IgE to Cells
    LAWRENCE BARRY SCHWARTZ; Fiscal Year: 2012
  10. Bayar Thimmapaya; Fiscal Year: 2016

Detail Information

Publications411 found, 100 shown here

  1. ncbi DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:5858-68. 1998
    ..Thus, gamma-H2AX formation is a rapid and sensitive cellular response to the presence of DNA double-stranded breaks, a response that may provide insight into higher order chromatin structures...
  2. ncbi Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
    D D Sarbassov
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 307:1098-101. 2005
    ..Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation...
  3. ncbi Plant stomata function in innate immunity against bacterial invasion
    Maeli Melotto
    Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
    Cell 126:969-80. 2006
    ..We provide evidence that supports a model in which stomata, as part of an integral innate immune system, act as a barrier against bacterial infection...
  4. ncbi Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
    Alexander Zimprich
    Department of Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tubingen, 72076 Tubingen, Germany
    Neuron 44:601-7. 2004
    ..Hence, LRRK2 may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism...
  5. ncbi The protein kinase complement of the human genome
    G Manning
    SUGEN Inc, 230 East Grand Avenue, South San Francisco, CA 94080, USA
    Science 298:1912-34. 2002
    ..We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons...
  6. ncbi Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease
    Coro Paisan-Ruiz
    Unitat de Genetica Molecular, Departament de Genòmica i Proteòmica, Institut de Biomedicina de València CSIC, E46010 Valencia, Spain
    Neuron 44:595-600. 2004
    ..Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor...
  7. pmc A global protein kinase and phosphatase interaction network in yeast
    Ashton Breitkreutz
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada
    Science 328:1043-6. 2010
    The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation...
  8. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
    ..Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity...
  9. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
    ..Our data indicate a molecular mechanism for TSC2 in insulin signalling, tumour suppressor functions and in the inhibition of cell growth...
  10. ncbi Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
    Ira E Clark
    Nature 441:1162-6. 2006
    ..The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis...
  11. ncbi Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence
    Nikolaj Blom
    Center for Biological Sequence Analysis, The Technical University of Denmark, Lyngby, Denmark
    Proteomics 4:1633-49. 2004
    ..The new server, NetPhosK, is made publicly available at the URL http://www.cbs.dtu.dk/services/NetPhosK/. The issues of underestimation, over-prediction and strategies for improving prediction specificity are also discussed...
  12. ncbi Bacterial disease resistance in Arabidopsis through flagellin perception
    Cyril Zipfel
    Friedrich Miescher Institute for Biomedical Research, PO Box 2543, CH 4002 Basel, Switzerland
    Nature 428:764-7. 2004
    ..tomato DC3000 when it is sprayed on the leaf surface. Thus, flagellin perception restricts bacterial invasion, probably at an early step, and contributes to the plant's disease resistance...
  13. ncbi Growing roles for the mTOR pathway
    Dos D Sarbassov
    Whitehead Institute, MIT Department of Biology, 9 Cambridge Center, Cambridge, Massachussetts 02142, USA
    Curr Opin Cell Biol 17:596-603. 2005
    ....
  14. ncbi Two-component signal transduction
    A M Stock
    Center for Advanced Biotechnology and Medicine and Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Annu Rev Biochem 69:183-215. 2000
    ..Thus detailed analyses of a relatively small number of representative proteins provide a foundation for understanding this large family of signaling proteins...
  15. ncbi Upstream and downstream of mTOR
    Nissim Hay
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 60607, USA
    Genes Dev 18:1926-45. 2004
    ..We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity...
  16. doi PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
    Sven Geisler
    Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
    Nat Cell Biol 12:119-31. 2010
    ..Thus, our data provide functional links between PINK1, Parkin and the selective autophagy of mitochondria, which is implicated in the pathogenesis of Parkinson's disease...
  17. ncbi The protein kinase family: conserved features and deduced phylogeny of the catalytic domains
    S K Hanks
    Molecular Biology Laboratory, Salk Institute for Biological Studies, San Diego, CA 92138
    Science 241:42-52. 1988
    ..Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members...
  18. ncbi Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton
    D D Sarbassov
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Curr Biol 14:1296-302. 2004
    ..We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals...
  19. ncbi MAP kinase signalling cascade in Arabidopsis innate immunity
    Tsuneaki Asai
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 415:977-83. 2002
    ..Activation of this MAPK cascade confers resistance to both bacterial and fungal pathogens, suggesting that signalling events initiated by diverse pathogens converge into a conserved MAPK cascade...
  20. ncbi Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase
    M Maekawa
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606 8315, Japan
    Science 285:895-8. 1999
    ..These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton...
  21. ncbi hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts
    Shian Wu
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Cell 114:445-56. 2003
    ..A human homolog of hpo completely rescues the overgrowth phenotype of Drosophila hpo mutants, suggesting that hpo might play a conserved role for growth control in mammals...
  22. ncbi mTOR and cancer: insights into a complex relationship
    David M Sabatini
    Whitehead Institute for Biomedical Research, MIT Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142 1479, USA
    Nat Rev Cancer 6:729-34. 2006
    ..The purpose is not to cover all aspects of mTOR history and signalling, but rather to foster discussion by presenting some occasionally provocative ideas...
  23. pmc Differential innate immune signalling via Ca(2+) sensor protein kinases
    Marie Boudsocq
    Department of Genetics, Harvard Medical School, Center for Computational and Integrative Biology, Massachusetts General Hospital, Massachusetts 02114, USA
    Nature 464:418-22. 2010
    ..functional genomic screen and genome-wide gene expression profiling, here we show that four calcium-dependent protein kinases (CDPKs) are Ca(2+)-sensor protein kinases critical for transcriptional reprogramming in plant innate immune ..
  24. pmc PINK1 is selectively stabilized on impaired mitochondria to activate Parkin
    Derek P Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    PLoS Biol 8:e1000298. 2010
    ..In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination...
  25. ncbi Chk1 and Chk2 kinases in checkpoint control and cancer
    Jiri Bartek
    Department of Cell Cycle and Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
    Cancer Cell 3:421-9. 2003
    ....
  26. ncbi The TOR pathway: a target for cancer therapy
    Mary Ann Bjornsti
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Cancer 4:335-48. 2004
  27. ncbi mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
    Do Hyung Kim
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell 110:163-75. 2002
    ..We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels...
  28. pmc The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 320:1496-501. 2008
    ..The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb...
  29. pmc PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility
    Xinnan Wang
    F M Kirby Neurobiology Center, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 147:893-906. 2011
    ..PINK1 has been shown to act upstream of Parkin, but the mechanism corresponding to this relationship has not been known. We propose that PINK1 phosphorylation of substrates triggers the subsequent action of Parkin and the proteasome...
  30. pmc Comparative analysis of the receptor-like kinase family in Arabidopsis and rice
    Shin Han Shiu
    Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA
    Plant Cell 16:1220-34. 2004
    ..These findings led us to hypothesize that most of the recent expansions of the RLK/Pelle family have involved defense/resistance-related genes...
  31. ncbi A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence
    Delphine Chinchilla
    Zurich Basel Plant Science Center, Botanical Institute, University of Basel, Hebelstrasse 1, 4056 Basel, Switzerland
    Nature 448:497-500. 2007
    ..Thus, BAK1 is not only associated with developmental regulation through the plant hormone receptor BRI1 (refs 6,7), but also has a functional role in PRR-dependent signalling, which initiates innate immunity...
  32. pmc Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL
    Seok Min Jin
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 191:933-42. 2010
    ..Thus, differential localization to the inner and outer mitochondrial membranes appears to regulate PINK1 stability and function...
  33. pmc Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission
    Ruben K Dagda
    Department of Pathology and Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 284:13843-55. 2009
    ..Furthermore, PINK1 and Parkin may cooperate through different mechanisms to maintain mitochondrial homeostasis...
  34. ncbi TOR, a central controller of cell growth
    T Schmelzle
    Department of Biochemistry, Biozentrum, University of Basel, Switzerland
    Cell 103:253-62. 2000
    ....
  35. pmc Patterns of somatic mutation in human cancer genomes
    Christopher Greenman
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Nature 446:153-8. 2007
    ..Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated...
  36. ncbi Mitotic kinases as regulators of cell division and its checkpoints
    E A Nigg
    Max Planck Institute for Biochemistry, Department of Cell Biology, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Nat Rev Mol Cell Biol 2:21-32. 2001
    ..Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission...
  37. pmc PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
    Cristofol Vives-Bauza
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 107:378-83. 2010
    ..Thus by impairing this process, mutations in either Parkin or PINK1 may alter mitochondrial turnover which, in turn, may cause the accumulation of defective mitochondria and, ultimately, neurodegeneration in Parkinson's disease...
  38. pmc Arabidopsis OST1 protein kinase mediates the regulation of stomatal aperture by abscisic acid and acts upstream of reactive oxygen species production
    Anna Chiara Mustilli
    Institut des Sciences du Vegetal, Centre National de la Recherche Scientifique, Unité Propre de Recherche 2355, 91190 Gif sur Yvette, France
    Plant Cell 14:3089-99. 2002
    ..These results suggest that OST1 acts in the interval between ABA perception and ROS production. The relative positions of ost1 and the other ABA-insensitive mutations in the ABA signaling network (abi1-1, abi2-1, and gca2) are discussed...
  39. pmc The Arabidopsis CDPK-SnRK superfamily of protein kinases
    Estelle M Hrabak
    Department of Plant Biology and Program in Genetics, University of New Hampshire, 46 College Road, Durham 03824, USA
    Plant Physiol 132:666-80. 2003
    The CDPK-SnRK superfamily consists of seven types of serine-threonine protein kinases: calcium-dependent protein kinase (CDPKs), CDPK-related kinases (CRKs), phosphoenolpyruvate carboxylase kinases (PPCKs), PEP carboxylase kinase-related ..
  40. pmc The PINK1/Parkin pathway regulates mitochondrial morphology
    Angela C Poole
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 105:1638-43. 2008
    ..Our studies suggest that the PINK1/Parkin pathway promotes mitochondrial fission and that the loss of mitochondrial and tissue integrity in PINK1 and parkin mutants derives from reduced mitochondrial fission...
  41. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003
    ..Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling...
  42. pmc PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65
    Chandana Kondapalli
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Open Biol 2:120080. 2012
    ..Our findings also suggest that small molecule activators of Parkin that mimic the effect of PINK1 phosphorylation may confer therapeutic benefit for PD...
  43. ncbi The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases
    Rebecca L Hurley
    Departments of Medicine and Biochemistry, Dartmouth Medical School and the Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA
    J Biol Chem 280:29060-6. 2005
    ..These data indicate that the CaMKKs function in intact cells as AMPKKs, predicting wider roles for these kinases in regulating AMPK activity in vivo...
  44. ncbi Current development of mTOR inhibitors as anticancer agents
    Sandrine Faivre
    Service Inter Hospitalier de Cancrologie, Beaujon University Hospital, 100 Boulevard du General Leclerc, 92118 Clichy Cedex, France
    Nat Rev Drug Discov 5:671-88. 2006
    ..Here we review the clinical development of this drug class and look at future prospects for incorporating these agents into multitarget or multimodality strategies against cancer...
  45. pmc Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin
    Michael Lazarou
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Dev Cell 22:320-33. 2012
    ..We propose that the association of PINK1 with the TOM complex allows rapid reimport of PINK1 to rescue repolarized mitochondria from mitophagy, and discount mitochondrial-specific factors for Parkin translocation and activation...
  46. pmc Arabidopsis cytokinin receptor mutants reveal functions in shoot growth, leaf senescence, seed size, germination, root development, and cytokinin metabolism
    Michael Riefler
    Institute of Biology Applied Genetics, Free University of Berlin, Germany
    Plant Cell 18:40-54. 2006
    ....
  47. ncbi Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma
    Gary Hudes
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    N Engl J Med 356:2271-81. 2007
    ..Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease...
  48. ncbi Sch9 is a major target of TORC1 in Saccharomyces cerevisiae
    Jörg Urban
    Department of Molecular Biology, University of Geneva, Geneva, CH 1211, Switzerland
    Mol Cell 26:663-74. 2007
    ..Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt...
  49. ncbi Evolution of protein kinase signaling from yeast to man
    Gerard Manning
    Sugen Inc 230 East Grand Ave, South San Francisco, CA 94080, USA
    Trends Biochem Sci 27:514-20. 2002
    ....
  50. ncbi The conformational plasticity of protein kinases
    Morgan Huse
    Department of Biological Sciences, Stanford University, Palo Alto, California 94305, USA
    Cell 109:275-82. 2002
    b>Protein kinases operate in a large number of distinct signaling pathways, where the tight regulation of their catalytic activity is crucial to the development and maintenance of eukaryotic organisms...
  51. ncbi TOR signaling in growth and metabolism
    Stephan Wullschleger
    Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Cell 124:471-84. 2006
    ..The physiological consequences of mammalian TORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders...
  52. pmc Elucidation of a universal size-control mechanism in Drosophila and mammals
    Jixin Dong
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 130:1120-33. 2007
    ..These results uncover a universal size-control mechanism in metazoan...
  53. ncbi Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2
    J Gyuris
    Department of Molecular Biology, Massachusetts General Hospital, Boston 02114
    Cell 75:791-803. 1993
    ..These experiments identify Cdi1 as a novel type of protein phosphatase that forms complexes with cyclin-dependent kinases...
  54. pmc ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1
    H Zhao
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110 1093, USA
    Mol Cell Biol 21:4129-39. 2001
    ..In addition, this study implicates ATR as a direct upstream activator of Chk1 in human cells...
  55. pmc Calcium signaling through protein kinases. The Arabidopsis calcium-dependent protein kinase gene family
    Shu Hua Cheng
    Department of Genetics, Harvard Medical School, MA 02114, USA
    Plant Physiol 129:469-85. 2002
    In plants, numerous Ca(2+)-stimulated protein kinase activities occur through calcium-dependent protein kinases (CDPKs)...
  56. pmc Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint
    Tony S Byun
    Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305, USA
    Genes Dev 19:1040-52. 2005
    ....
  57. pmc Two calcium-dependent protein kinases, CPK4 and CPK11, regulate abscisic acid signal transduction in Arabidopsis
    Sai Yong Zhu
    China State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, 100094 Beijing, China
    Plant Cell 19:3019-36. 2007
    Many biochemical approaches show functions of calcium-dependent protein kinases (CDPKs) in abscisic acid (ABA) signal transduction, but molecular genetic evidence linking defined CDPK genes with ABA-regulated biological functions at the ..
  58. pmc Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus)
    Jason E Stajich
    Department of Plant Pathology and Microbiology, University of California, Riverside, CA 92521, USA
    Proc Natl Acad Sci U S A 107:11889-94. 2010
    ..contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi...
  59. pmc PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy
    Noriyuki Matsuda
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    J Cell Biol 189:211-21. 2010
    ..Some pathogenic mutations of PINK1 and Parkin interfere with the aforementioned events, suggesting an etiological importance. These results provide crucial insight into the pathogenic mechanisms of PD...
  60. ncbi The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP
    Jianbin Huang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Cell 122:421-34. 2005
    ..Thus, Yki is a critical target of the Wts/Lats protein kinase and a potential oncogene...
  61. pmc Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint
    Q Liu
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:1448-59. 2000
    ..Taken together, these data indicate that Chk1 plays an essential role in the mammalian DNA damage checkpoint, embryonic development, and tumor suppression, and that Atr regulates Chk1...
  62. ncbi FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis
    L Gomez-Gomez
    Friedrich Miescher Institut, Basel, Switzerland
    Mol Cell 5:1003-11. 2000
    ..FLS2 shares structural and functional homologies with known plant resistance genes and with components involved in the innate immune system of mammals and insects...
  63. ncbi A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction
    J Li
    Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Cell 90:929-38. 1997
    ..The extracellular domain contains 25 tandem leucine-rich repeats that resemble repeats found in animal hormone receptors, plant disease resistance genes, and genes involved in unknown signaling pathways controlling plant development...
  64. ncbi Binding of brassinosteroids to the extracellular domain of plant receptor kinase BRI1
    Toshinori Kinoshita
    Howard Hughes Medical Institute and Plant Biology Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Road, La Jolla, California 92037, USA
    Nature 433:167-71. 2005
    ..Our results demonstrate that brassinosteroids bind directly to the 94 amino acids comprising ID-LRR22 in the extracellular domain of BRI1, and define a new binding domain for steroid hormones...
  65. ncbi Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1
    F Urano
    Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA
    Science 287:664-6. 2000
    ..Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals...
  66. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
    ..Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders...
  67. ncbi Hereditary early-onset Parkinson's disease caused by mutations in PINK1
    Enza Maria Valente
    CSS IRCCS, Mendel Institute, Viale Regina Margherita 261, 00198 Rome, Italy
    Science 304:1158-60. 2004
    ..These data provide a direct molecular link between mitochondria and the pathogenesis of PD...
  68. pmc Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
    Bin Zhao
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    Genes Dev 21:2747-61. 2007
    ..Our observations demonstrate that YAP plays a key role in the Hippo pathway to control cell proliferation in response to cell contact...
  69. pmc Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2
    H Christian Reinhardt
    David H Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Curr Opin Cell Biol 21:245-55. 2009
    ..Here we will discuss recent advances in our understanding of the eukaryotic DNA damage response with emphasis on the Chk1, Chk2, and the newly emerged effector kinases p38MAPK and MK2...
  70. doi Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics
    Cynthia X Ma
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Trends Mol Med 17:88-96. 2011
    ..In this review, we summarize recent advances and controversies in the development and application of CHK1 inhibitors as cancer therapeutics...
  71. pmc Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress
    Clement A Gautier
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:11364-9. 2008
    ....
  72. ncbi Defining the role of mTOR in cancer
    David A Guertin
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02141, USA
    Cancer Cell 12:9-22. 2007
    ..We further discuss the use of rapamycin in oncology and conclude with a discussion on the future of mTOR-targeted therapy...
  73. doi Targeting cancer with small molecule kinase inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:28-39. 2009
    ..This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors...
  74. pmc Large-scale Arabidopsis phosphoproteome profiling reveals novel chloroplast kinase substrates and phosphorylation networks
    Sonja Reiland
    Department of Biology, Eidgenossische Technische Hochschule Zurich, 8092 Zurich, Switzerland
    Plant Physiol 150:889-903. 2009
    ..We propose that ATP synthase is regulated in cooperation with 14-3-3 proteins by CKII-mediated phosphorylation of ATP synthase beta-subunit in the dark...
  75. ncbi Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
    Brinda Ravikumar
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Genet 36:585-95. 2004
    ..Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease...
  76. ncbi Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies
    O Jameel Shah
    Molecular and Cellular Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Biol 14:1650-6. 2004
    ..Our results suggest that inappropriate activation of the Rheb/mTOR/S6K pathway imposes a negative feedback program to attenuate IRS-dependent processes such as cell survival...
  77. ncbi Perception of the bacterial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation
    Cyril Zipfel
    Botanical Institute, Zurich Basel Plant Science Centre, University of Basel, Hebelstrasse 1, CH 4056 Basel, Switzerland
    Cell 125:749-60. 2006
    ..These results demonstrate that EFR is the EF-Tu receptor and that plant defense responses induced by PAMPs such as EF-Tu reduce transformation by Agrobacterium...
  78. pmc Biological insights from structures of two-component proteins
    Rong Gao
    Center for Advanced Biotechnology and Medicine, Department of Biochemistry, UMDNJ Robert Wood Johnson Medical School and Howard Hughes Medical Institute, Piscataway, New Jersey 08854 5627, USA
    Annu Rev Microbiol 63:133-54. 2009
    ....
  79. ncbi A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools
    X Zhao
    Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, New York 10032 2704, USA
    Mol Cell 2:329-40. 1998
    ..Finally, both in vivo and in vitro experiments show that Sml1 binds to Rnr1. We propose that Sml1 inhibits dNTP synthesis posttranslationally by binding directly to Rnr1 and that Mec1 and Rad53 are required to relieve this inhibition...
  80. pmc The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission
    Rita Tewari
    Institute of Genetics, QMC, University of Nottingham, Nottingham NG7 2UH, UK
    Cell Host Microbe 8:377-87. 2010
    Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development...
  81. pmc Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment
    Andrew W Greene
    McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    EMBO Rep 13:378-85. 2012
    ..These results highlight a new role for MPP in PINK1 import and mitochondrial quality control via the PINK1–Parkin pathway...
  82. pmc p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage
    H Christian Reinhardt
    Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18 580, Cambridge, MA 02139, USA
    Cancer Cell 11:175-89. 2007
    ..We show that the Chk1 inhibitor UCN-01 also potently inhibits MK2, suggesting that its clinical efficacy results from the simultaneous disruption of two critical checkpoint pathways in p53-defective cells...
  83. ncbi Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin
    Nicole Exner
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 27:12413-8. 2007
    ..Our results may therefore suggest that PINK1 deficiency in humans results in mitochondrial abnormalities associated with cellular stress, a pathological phenotype, which can be ameliorated by enhanced expression of parkin...
  84. pmc Protein kinases: evolution of dynamic regulatory proteins
    Susan S Taylor
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
    Trends Biochem Sci 36:65-77. 2011
    Eukayotic protein kinases evolved as a family of highly dynamic molecules with strictly organized internal architecture. A single hydrophobic F-helix serves as a central scaffold for assembly of the entire molecule...
  85. pmc PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death
    Sonia Gandhi
    Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, UK
    Mol Cell 33:627-38. 2009
    ..Our findings propose a mechanism by which PINK1 dysfunction renders neurons vulnerable to cell death...
  86. doi Comprehensive analysis of kinase inhibitor selectivity
    Mindy I Davis
    Ambit Biosciences, San Diego, California, USA
    Nat Biotechnol 29:1046-51. 2011
    ..Our findings will help to realize the direct enabling potential of genomics for drug development and basic research about cellular signaling...
  87. doi A spatial gradient coordinates cell size and mitotic entry in fission yeast
    James B Moseley
    The Rockefeller University, New York, New York 10065, USA
    Nature 459:857-60. 2009
    ..We propose that the Pom1 polar gradient and the medial cortical nodes generate information about cell size and coordinate this with mitotic entry by regulating Cdk1 through Pom1, Cdr2, Cdr1 and Wee1...
  88. ncbi Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization
    N Yang
    Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
    Nature 393:809-12. 1998
    ..Furthermore, insulin and an active form of Rac increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1 participates in Rac-mediated actin cytoskeletal reorganization, probably by phosphorylating cofilin...
  89. ncbi mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways
    Pradip K Majumder
    Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Med 10:594-601. 2004
    ....
  90. ncbi The LKB1 tumor suppressor negatively regulates mTOR signaling
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    Cancer Cell 6:91-9. 2004
    ..These findings position aberrant mTOR activation at the nexus of these germline neoplastic conditions and suggest the use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome...
  91. pmc Evidence that entry into sporulation in Bacillus subtilis is governed by a gradual increase in the level and activity of the master regulator Spo0A
    Masaya Fujita
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Genes Dev 19:2236-44. 2005
    ..Evidence indicates that this gradual increase in Spo0A protein and activity plays a critical role in triggering sporulation and requires the action of the phosphorelay...
  92. pmc G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer
    N Bucher
    Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    Br J Cancer 98:523-8. 2008
    ....
  93. ncbi Identification of CRE1 as a cytokinin receptor from Arabidopsis
    T Inoue
    Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Japan
    Nature 409:1060-3. 2001
    ..10), providing direct evidence that CRE1 is a cytokinin receptor. We also provide evidence that cytokinins can activate CRE1 to initiate phosphorelay signalling...
  94. ncbi The kinase domain of titin controls muscle gene expression and protein turnover
    Stephan Lange
    Muscle Signalling and Development, Randall Division, King s College London, London SE1 1UL, UK
    Science 308:1599-603. 2005
    ..A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway...
  95. pmc PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding
    Michael Lazarou
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 200:163-72. 2013
    ..Self-association occurred independent of ubiquitination activity through the RING-between-RING domain, providing mechanistic insight into how PINK1 activates Parkin...
  96. pmc DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains
    Xiaochun Yu
    Department of Oncology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Mol Cell Biol 24:9478-86. 2004
    ..Taken together, these data not only implicate CtIP as a critical player in cell cycle checkpoint control but also provide molecular mechanisms by which BRCA1 controls multiple cell cycle transitions after DNA damage...
  97. pmc A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers
    J R Bischoff
    SUGEN, Inc, Redwood City, California 94063, USA
    EMBO J 17:3052-65. 1998
    ..These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy...
  98. doi Hypoxia: a window into Mycobacterium tuberculosis latency
    Tige R Rustad
    Seattle Biomedical Research Institute, Seattle, WA, USA
    Cell Microbiol 11:1151-9. 2009
    ..tuberculosis hypoxic responses. We also examine the role of these responses in tuberculosis latency, and identify promising avenues for future studies...
  99. ncbi Novel domains of the prokaryotic two-component signal transduction systems
    M Y Galperin
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
    FEMS Microbiol Lett 203:11-21. 2001
    ..It appears that the real picture of the complexity of phosphorelay signal transduction in prokaryotes is only beginning to unfold...
  100. ncbi The phosphoinositide 3-kinase pathway
    Lewis C Cantley
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115 5713, USA
    Science 296:1655-7. 2002
    ..The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention...
  101. ncbi mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes
    Richard C Hresko
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:40406-16. 2005
    ..Based on our cell-free kinase and small interference RNA results, we conclude that mTOR complexed to RICTOR is the Ser-473 kinase in 3T3-L1 adipocytes...

Research Grants77

  1. Xenoestrogen regulation of Leydig cells
    BENSON TOKUNBO AKINGBEMI; Fiscal Year: 2010
    ..epidermal growth factor receptors (EGFR), insulin growth factor-1 receptors (IGF-1R) and mitogen activated protein kinases (MAPK) (Aim II);and, Action of soy isoflavones in Sertoli cells affects Leydig cells (Aim III)...
  2. Cory Teuscher; Fiscal Year: 2014
    ....
  3. Role of Chromogranin A in Metabolic Syndrome
    Sushil K Mahata; Fiscal Year: 2013
    ..2. Evaluate the potential therapeutic effects of CST and its variants on insulin sensitivity and baroreflex sensitivity and heart rate variability in high fat diet-induced insulin resistant and in db/db diabetic mice. ..
  4. VINCENT SCOTT TAGLIABRACCI; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Research: Protein phosphorylation by protein kinases is an important regulatory mechanism that influences every aspect of cellular life...
  5. Emilio B Gonzalez; Fiscal Year: 2014
    ..These studies may help to devise new more specific and less harmful modalities than the anticoagulation or general immunosuppression currently used to treat and prevent thrombosis in patients with aPL Abs. ..
  6. CLIFFORD RUSSELL GREYSON; Fiscal Year: 2016
    ..Agents with potential clinical utility will be identified using the isolated papillary muscle model and tested in the pig model. ..
  7. JAMES RUSSELL SOWERS; Fiscal Year: 2015
    ..A better understanding of factors involved in insulin resistance should help in the development of therapeutic targets to help prevent diabetes and cardiovascular disease. ..
  8. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): WNK (With No lysine (K)) protein kinases are Ste20 relatives that we discovered through studying control of mitogen-activated protein kinases (MAPKs)...
  9. Cellular &Inflammatory Pathways in Ashtma &Allergic Diseases: From IgE to Cells
    LAWRENCE BARRY SCHWARTZ; Fiscal Year: 2012
    ..Understanding more precisely the characteristics of and the mechanism(s) behind desensitization will enable physicians to better utilize this approach to reduce mast cell/basophil-mediated contributions to asthma and allergic diseases. ..
  10. Bayar Thimmapaya; Fiscal Year: 2016
    ....
  11. Patient-Derived Stem Cells for Phosphoproteomic Profiling Neuropsychopathology
    Dieter A Wolf; Fiscal Year: 2011
    ....
  12. Trichothecene Toxicity and the Ribotoxic Stress Response
    James J Pestka; Fiscal Year: 2012
    ..Although ribosome-directed agents are known to exert toxicity by activating mitogen-activated protein kinases, the underlying mechanisms for this "ribotoxic stress response" (RSR) remain largely undefined...
  13. Kazem M Azadzoi; Fiscal Year: 2016
    ..abstract_text> ..
  14. Inderjit Singh; Fiscal Year: 2014
    ....
  15. John S Davis; Fiscal Year: 2014
    ..Considering the importance sex steroids in health and disease, we must have a better understanding of the mechanisms controlling the synthesis of steroid hormones. ..
  16. DAVID MATTHEW KELLER; Fiscal Year: 2016
    ..This proposal will characterize a new target of cAMP signaling, microRNA-375, which has the potential to be used as a complementary therapy to enhance the efficacy of existing therapeutics that target the cAMP signaling pathway. ..
  17. MARK L DELL'ACQUA; Fiscal Year: 2016
    ....
  18. Subhash C Pandey; Fiscal Year: 2014
    ....
  19. The Relationship Between STK39, Salt Sensitivity, and HCTZ-induced BP Response
    YEN PEI CHRISTY CHANG; Fiscal Year: 2010
    ....
  20. Hybrid Katp Channel Opener and Redox Catalyst for Lung Transplantation
    Prakash Jagtap; Fiscal Year: 2013
    ..points: at 1 h post reperfusion for IkB[unreadable], nuclear p50, and phosphorylation of mitogen activated protein kinases (MAPKs - ERK, p38, JNK);at 3h post reperfusion for RT-PCR to quantify lung tissue mRNA concentrations of TNF-[..
  21. Mary K Sheats; Fiscal Year: 2016
    ....
  22. JoAnn Sekiguchi; Fiscal Year: 2014
    ..abstract_text> ..
  23. Mechanisms of Endothelin 1-Induced Sickle Cell Pathology
    Alicia Rivera; Fiscal Year: 2011
    ..We plan to characterize mechanisms of ET-1-stimulated sickle red cell dehydration as a means to develop ET-1 receptor antagonists as a novel therapy in the treatment of sickle cell disease. ..
  24. Alzheimer's Disease Therapeutic
    Trevor P Castor; Fiscal Year: 2012
    ..Alternatively, at this stage, Amylon will merge with a mid-tier public company or be acquired by a multinational pharmaceutical company. ..
  25. Biochemistry and Function of a Novel Bacterial Photosensory Two-Component System
    MELISSA MARKS; Fiscal Year: 2010
    ..transitions in bacteria largely use two-component signal transduction systems, consisting of histidine protein kinases and their cognate response regulator proteins. We have evidence that C...
  26. Nitric Oxide in Hemodialysis AV Fistula Maturation
    Richard A Cohen; Fiscal Year: 2010
    ....
  27. MARK REID PHILIPS; Fiscal Year: 2015
    ..We propose to study the cell biology and physiology of K-Ras phosphorylation to better understand how to exploit this process to develop anti-cancer drugs. ..
  28. RAJESH K ANEJA; Fiscal Year: 2016
    ..Additional studies will be performed to determine the therapeutic window for use of PARP-1 inhibitors in murine sepsis. ..
  29. Mitochondrial and Nuclear Mechanisms of Estrogen Receptor-Mediated Cardioprotecti
    DONNA HOPE KORZICK; Fiscal Year: 2012
    ..e. use of estrogen receptor therapeutics as viable approaches to improve ischemic tolerance in aged women. ..
  30. Analysis of the role of the VRK1 protein kinase in mammalian fertility
    Paula Traktman; Fiscal Year: 2011
    ..Dynamic protein phosphorylation, mediated by protein kinases and phosphatases, is one of the major mechanisms used by eukaryotic cells to ensure that the phases of ..
  31. Subhash C Pandey; Fiscal Year: 2016
    ..kinase B (trkB)-linked signaling [cAMP responsive-element binding protein (CREB) and extracellular regulated protein kinases 1/2 (Erk1/2)] are regulated and if BDNF signaling modulates synaptic plasticity in the amygdala resulting in ..
  32. JAMES RUSSELL SOWERS; Fiscal Year: 2016
    ..tyrosine (p) and the resultant downstream IRS-1/PI3-K/Akt signaling. ..
  33. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
    ....
  34. Robert V Farese; Fiscal Year: 2016
    ..abstract_text> ..
  35. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ..ubiquitination of TRAF6 plays a key role in its mechanism of action by creating a docking site for cytosolic protein kinases that relay immunoreceptor signals to transcription factors NF-?B and AP-1...
  36. Tatiana Efimova; Fiscal Year: 2014
    ..We are optimistic that the completion of the proposed studies will result in a better mechanistic understanding of the p384 role in epithelial carcinogenesis and its potential as an anti-cancer therapeutic target. ..
  37. ERIC KIRK LAU; Fiscal Year: 2014
    ..abstract_text> ..
  38. Mechanisms of Angiogenesis in Retinopathy of Prematurity
    Mary Elizabeth Hartnett; Fiscal Year: 2009
    ..g., dihydroethidium);and NADPH oxidase activation. ..
  39. Marcus Kaul; Fiscal Year: 2016
    ....
  40. Intermediary Metabolism, Histone Acetylation, and Transcriptional Regulation
    Ales Vancura; Fiscal Year: 2013
    ..In addition, this project will provide an excellent research environment for undergraduate and graduate students, as they prepare for careers in biomedical research. ..
  41. Novel CTD inhibitors with synthetic lethality to oncogenic Ras for cancer therapy
    Bingliang Fang; Fiscal Year: 2013
    ..The goal of this proposal is to perform pre-clinical studies on their antitumor activities in lung cancer cells in vitro and in vivo that are required for future clinical trials. ..
  42. KATHERINE JULIA KELLY; Fiscal Year: 2014
    ..Nearly one-half of patient beginning dialysis for CKD were e65 yo. We propose to study inflammatory and vascular injury and cell death and the effects of potential therapies in a model of CKD. ..
  43. KCNQ Channels and Vasoconstrictor Signal Transduction
    Kenneth L Byron; Fiscal Year: 2013
    ....
  44. Novel Regenerative Therapy for Myocardial Infarction
    Andrew R Mendelsohn; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE: We are developing a new regenerative therapy for the treatment of myocardial infarction (heart attacks). A new drug will stimulate the heart to repair itself. ..
  45. MARY ELIZABETH RUTH HARTNETT; Fiscal Year: 2016
    ..g., dihydroethidium);and NADPH oxidase activation. ..
  46. Andrew H Miller; Fiscal Year: 2014
    ..abstract_text> ..
  47. Structural biology of enzymes in fatty acid metabolism
    Liang Tong; Fiscal Year: 2012
    ....
  48. 14th International Workshop on Ataxia-Telangiectasia and ATM
    Richard A Gatti; Fiscal Year: 2010
    ..369 kDa) protein, ATM, which is a member of the phosphatidyl inositol 3 kinase family of serine/threonine protein kinases. The major role of ATM appears to be in the recognition and repair of double strand DNA breaks, through ..
  49. Gregory L Stahl; Fiscal Year: 2016
    ..Furthermore, these specific aims may subsequently lead to improved risk stratification, resource utilization, and the development of novel anti-complement therapies to protect against hyperglycemic cardiovascular complications. ..
  50. Michael W Schwartz; Fiscal Year: 2016
    ..By improving our understanding of how mechanisms driving obesity and diabetes are linked to one another within the brain, our ultimate goal is to find new strategies for their prevention and treatment. ..
  51. Claude A Piantadosi; Fiscal Year: 2016
    ..Understanding these fundamental regulatory mechanisms is needed to design forward-thinking therapeutic approaches to protect mitochondrial quality control during sepsis. ..
  52. Robert F Foronjy; Fiscal Year: 2014
    ..While a significant body of research has elucidated the role that protein kinases exert in this process, much less is known about the effects of protein phosphatases...
  53. Beta-cell Proliferation
    Fredric E Wondisford; Fiscal Year: 2013
    ..These studies of in vivo mechanisms of [unreadable]-cell proliferation may provide therapeutic approaches for diabetes mellitus in humans. ..
  54. PKC delta and cell renewal in irradiated taste epithelium
    MARY ELAINE REYLAND; Fiscal Year: 2012
    ..Understanding how taste loss occurs will enable the development of therapeutic strategies to reverse or prevent taste loss and improve the quality of life of patients undergoing head and neck irradiation. ..
  55. AKAP Regulation of PKA Targeting in the Heart
    Meredith Bond; Fiscal Year: 2009
    ..Our project investigates a novel nuclear AKAP protein, Chd8 that may participate in regulation of cardiac remodeling during ischemic heart failure. ..
  56. PHYSIOLOGY AND CLONING OF B FRAGILIS ENTEROTOXIN
    CYNTHIA SEARS; Fiscal Year: 2010
    ..including beta-catenin, gamma-secretase, tyrosine kinases, Nuclear Factor-kB (NF-kB) and mitogen-activated protein kinases (MARK) resulting in c-Myc induction, IEC proliferation with enhanced cellular migration and IEC secretion of ..
  57. Natasha N Chattergoon; Fiscal Year: 2016
    ..We will couple the results of B-Raf disruption to morphological, biochemical, and functional parameters of cardiac performance in the newborn and adult using echocardiographic measures. (End of Abstract) ..
  58. Role of TLR-4 in Lung Reperfusion Injury
    MICHAEL SCOTT MULLIGAN; Fiscal Year: 2013
    ..models of IRI have demonstrated that transcriptional factor activation is regulated by mitogen-activated protein kinases (MAPK), including ERK 1/2 and two stress-activated protein kinases (SAPK), JNK and p38...
  59. The role of LKB1 in the maintenance of genomic stability.
    Zhi Xiang Xu; Fiscal Year: 2013
    ..These studies will also provide rationale for pharmacologic replacement or mimicry of LKB1 function in cancer prevention and treatment. ..
  60. Role of Subdiaphragmatic Vagus in Fibromyalgia Syndrome
    JON DAVID LEVINE; Fiscal Year: 2013
    ..The findings should help tailor specific therapies that may prevent or at least ameliorate their significant suffering. ..
  61. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
    ..DNA damage usually evokes such checkpoints through activating a network of molecules including protein kinases ATM/ATR and their targets checkpoint kinases Chk1 and Chk2...
  62. Min Du; Fiscal Year: 2014
    ....
  63. Mechanisms of Splicing Regulation During Environmental Stress in Yeast
    Jaclyn C Greimann; Fiscal Year: 2012
    ..The goal of this research proposal is to understand the mechanisms regulating RNA splicing in response to environmental stress. ..
  64. Alexandra M Machikas; Fiscal Year: 2014
    ..Activation of receptor interacting protein kinases (RIP1 and RIP3) and formation of a necrosome in concert with Fas-associated death domain protein (FADD) and ..
  65. ADENOSINE AND ANTIOXIDANT ENZYMES
    Vickram Ramkumar; Fiscal Year: 1999
    ..Taken together, these studies will explore a novel mechanism of cytoprotection provided by adenosine and might contribute to the development of new treatments for myocardial and cerebral ischemia. ..
  66. MOLECULAR BASIS FOR DRUG INDUCED CARDIOTOXICITY IN AIDS
    CRAIG CLARKSON; Fiscal Year: 2001
    ....
  67. Protein Kinase D and Epidermal Structure and Function
    Wendy B Bollag; Fiscal Year: 2010
    ..This research should provide insight into the role of protein kinase D in skin structure and function and allow identification of new targets for the development of drugs to treat human skin diseases. ..
  68. CALMODULIN KINASE II AND ION TRANSPORT IN THE KIDNEY
    Rochelle Hanley; Fiscal Year: 1992
    ..These experiments should provide new information on the regulation of this protein kinase in the renal proximal convoluted tubule...
  69. OPIOID EFFECTS ON HYPOTHALAMIC NEURONAL EXCITABILITY
    Martin Kelly; Fiscal Year: 2002
    ....
  70. PROTEIN KINASE C AND PHOTORECEPTORS
    ALEXANDRA NEWTON; Fiscal Year: 2002
    ..Specifically, the effect of this phosphorylation on rhodopsin s macromolecular interactions (transducin coupling, arrestin binding) will be explored. ..
  71. MOLECULAR BIOLOGY OF BRAIN PROTEIN PHOSPHORYLATION
    James Sikela; Fiscal Year: 1993
    ..phosphorylation appears to play in brain function, very little is known regarding the genes encoding brain protein kinases, and even less is known about the true physiological role(s) such kinase fulfill in the brain...
  72. Protein Kinase B and C in Head Injury
    Larry Jenkins; Fiscal Year: 2007
    ....
  73. MYOCARDIAL PROTEIN KINASE C & B-ADRENOCEPTORS IN CHF
    Chang Seng Liang; Fiscal Year: 1990
    ....