intracellular signaling peptides and proteins

Summary

Summary: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.

Top Publications

  1. ncbi Notch signaling: cell fate control and signal integration in development
    S Artavanis-Tsakonas
    Massachusetts General Hospital Cancer Center, Department of Cell Biology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Science 284:770-6. 1999
  2. pmc 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks
    Samuel F Bunting
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 141:243-54. 2010
  3. ncbi TIGAR, a p53-inducible regulator of glycolysis and apoptosis
    Karim Bensaad
    The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Cell 126:107-20. 2006
  4. pmc Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
    Gina M DeNicola
    Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
    Nature 475:106-9. 2011
  5. pmc The hippo signaling pathway in development and cancer
    Duojia Pan
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Cell 19:491-505. 2010
  6. ncbi Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior
    T Sakurai
    Howard Hughes Medical Institute, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75235 9050, USA
    Cell 92:573-85. 1998
  7. pmc The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal
    Bin Zhao
    Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
    Nat Cell Biol 13:877-83. 2011
  8. 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
  9. 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
  10. ncbi Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism
    Vincenzo Bonifati
    Genetic Epidemiologic Unit, Department of Clinical Genetics, Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, Post Office Box 1738, 3000 DR Rotterdam, Netherlands
    Science 299:256-9. 2003

Detail Information

Publications273 found, 100 shown here

  1. ncbi Notch signaling: cell fate control and signal integration in development
    S Artavanis-Tsakonas
    Massachusetts General Hospital Cancer Center, Department of Cell Biology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Science 284:770-6. 1999
    ..Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis...
  2. pmc 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks
    Samuel F Bunting
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 141:243-54. 2010
    ..Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations...
  3. ncbi TIGAR, a p53-inducible regulator of glycolysis and apoptosis
    Karim Bensaad
    The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Cell 126:107-20. 2006
    ..The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage...
  4. pmc Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
    Gina M DeNicola
    Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
    Nature 475:106-9. 2011
    ..Thus, the Nrf2 antioxidant and cellular detoxification program represents a previously unappreciated mediator of oncogenesis...
  5. pmc The hippo signaling pathway in development and cancer
    Duojia Pan
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Cell 19:491-505. 2010
    ..These studies suggest that the core Hippo kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology...
  6. ncbi Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior
    T Sakurai
    Howard Hughes Medical Institute, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75235 9050, USA
    Cell 92:573-85. 1998
    ..prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior...
  7. pmc The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal
    Bin Zhao
    Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
    Nat Cell Biol 13:877-83. 2011
    ..In this review we summarize current understanding of the composition and regulation of the Hippo pathway, and discuss how cell polarity and cell adhesion proteins inform the role of this pathway in organ size control and regeneration...
  8. 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...
  9. 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...
  10. ncbi Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism
    Vincenzo Bonifati
    Genetic Epidemiologic Unit, Department of Clinical Genetics, Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, Post Office Box 1738, 3000 DR Rotterdam, Netherlands
    Science 299:256-9. 2003
    ..Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease...
  11. 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...
  12. pmc The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
    L de Lecea
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 95:322-7. 1998
    ..One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters...
  13. pmc ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery
    Chang Hwa Jung
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA
    Mol Biol Cell 20:1992-2003. 2009
    ..These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling...
  14. ncbi RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins
    Carsten Doil
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Copenhagen, Denmark
    Cell 136:435-46. 2009
    ..Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance...
  15. pmc Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2
    Akira Kobayashi
    Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences, and JST ERATO Environmental Response Project, University of Tsukuba, Tsukuba 305 8575, Japan
    Mol Cell Biol 24:7130-9. 2004
    ..To our knowledge, Nrf2 and Keap1 are the first reported mammalian substrate and adaptor, respectively, of the Cul3-based E3 ligase system...
  16. pmc 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers
    Peter Bouwman
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Nat Struct Mol Biol 17:688-95. 2010
    ..We find reduced 53BP1 expression in subsets of sporadic triple-negative and BRCA-associated breast cancers, indicating the potential clinical implications of our findings...
  17. ncbi Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution
    Keiko Taguchi
    Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2 1 Seiryo cho, Aoba ku, Sendai 980 8575, Japan
    Genes Cells 16:123-40. 2011
    ..Discovery and development of selective Nrf2 inhibitors should make a critical contribution to improved cancer therapy...
  18. pmc Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy
    Nao Hosokawa
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 20:1981-91. 2009
    ..ULK1 is dephosphorylated by rapamycin treatment or starvation. These data suggest that mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex...
  19. ncbi 53BP1-mediated DNA double strand break repair: insert bad pun here
    Angela T Noon
    Southern Alberta Cancer Research Institute, Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N4N1
    DNA Repair (Amst) 10:1071-6. 2011
    ....
  20. pmc Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma
    Mara Compagno
    Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA
    Nature 459:717-21. 2009
    ..Thus, our results demonstrate that NF-kappaB activation in DLBCL is caused by genetic lesions affecting multiple genes, the loss or activation of which may promote lymphomagenesis by leading to abnormally prolonged NF-kappaB responses...
  21. ncbi Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase)
    M Amano
    Division of Signal Transduction, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma 630 01
    J Biol Chem 271:20246-9. 1996
    ..The activated Rho-kinase subsequently phosphorylates MLC. This may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction...
  22. ncbi Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition
    C Du
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 102:33-42. 2000
    ..Overexpression of Smac increases cells' sensitivity to apoptotic stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that promotes apoptosis by activating caspases...
  23. pmc Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus
    Robert R Graham
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Nat Genet 40:1059-61. 2008
    ..These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA...
  24. ncbi Rocks: multifunctional kinases in cell behaviour
    Kirsi Riento
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, 91 Riding House Street, London W1W 7BS, UK
    Nat Rev Mol Cell Biol 4:446-56. 2003
    ..Recent experiments have defined new functions of ROCKs in cells, including centrosome positioning and cell-size regulation, which might contribute to various physiological and pathological states...
  25. ncbi De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling
    Ingrid E Wertz
    Department of Molecular Oncology, School of Medicine, University of California, Davis, Davis, California 95616, USA
    Nature 430:694-9. 2004
    ..We also provide an example of a protein containing separate ubiquitin ligase and DUB domains, both of which participate in mediating a distinct regulatory effect...
  26. 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...
  27. ncbi The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
    David L Boone
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
    Nat Immunol 5:1052-60. 2004
    ..The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells...
  28. 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...
  29. pmc Coupling of the nucleus and cytoplasm: role of the LINC complex
    Melissa Crisp
    Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610
    J Cell Biol 172:41-53. 2006
    ..2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex)...
  30. pmc RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites
    Frédérick A Mallette
    Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Sir Mortimer B Davis Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
    EMBO J 31:1865-78. 2012
    ..We propose that the RNF8-dependent degradation of JMJD2A regulates DNA repair by controlling the recruitment of 53BP1 at DNA damage sites...
  31. pmc Hippo signaling: growth control and beyond
    Georg Halder
    Department of Biochemistry and Molecular Biology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Development 138:9-22. 2011
    ....
  32. ncbi Negative regulation of toll-like receptor-mediated immune responses
    Foo Y Liew
    Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow G11 6NT, UK
    Nat Rev Immunol 5:446-58. 2005
    ..Here, we discuss the various negative regulatory mechanisms that have evolved to attenuate TLR signalling to maintain this immunological balance...
  33. ncbi Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
    M Uehata
    Discovery Research Tokyo, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan
    Nature 389:990-4. 1997
    ..Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically...
  34. ncbi Assembly and function of DNA double-strand break repair foci in mammalian cells
    Simon Bekker-Jensen
    Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen N, Denmark
    DNA Repair (Amst) 9:1219-28. 2010
    ..In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures...
  35. ncbi Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
    K Kimura
    Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630 01, Japan
    Science 273:245-8. 1996
    ..Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase...
  36. ncbi NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer
    John D Hayes
    Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK
    Trends Biochem Sci 34:176-88. 2009
    ..Moreover, constitutive NRF2 activation might cause drug resistance in tumours, and an understanding of how the transcription factor is regulated indicates ways in which this could be overcome...
  37. pmc Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex
    Donna D Zhang
    Department of Biochemistry, University of Missouri Columbia, M121 Medical Sciences Building, Columbia, MO 65212, USA
    Mol Cell Biol 24:10941-53. 2004
    ....
  38. ncbi The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Nat Cell Biol 12:213-23. 2010
    ....
  39. ncbi Inhibition of death receptor signals by cellular FLIP
    M Irmler
    Institute of Biochemistry, Lausanne Branch, University of Lausanne, Switzerland
    Nature 388:190-5. 1997
    ..High levels of FLIP(L) protein are also detectable in melanoma cell lines and malignant melanoma tumours. Thus FLIP may be implicated in tissue homeostasis as an important regulator of apoptosis...
  40. ncbi Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis
    Mats Hellstrom
    AngioGenetics Sweden AB, Scheeles vag 2, SE 171 77 Stockholm, Sweden
    Nature 445:776-80. 2007
    ....
  41. pmc Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks
    Yaron Galanty
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 462:935-9. 2009
    ..These findings thus identify PIAS1 and PIAS4 as components of the DDR and reveal how protein recruitment to DSB sites is controlled by coordinated SUMOylation and ubiquitylation...
  42. pmc Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation
    Tomomi Kiyomitsu
    Whitehead Institute, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Cell Biol 14:311-7. 2012
    ..We propose that these chromosome- and spindle-pole-derived gradients generate an intrinsic code to control spindle position and orientation...
  43. pmc DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy
    Kelly Jean Thomas
    Laboratory of Neurogenetics, National Institute on Aging, Flow Cytometry Core Facility, National Institutes of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20982 3707, USA
    Hum Mol Genet 20:40-50. 2011
    ..None of the three proteins complex together using size exclusion chromatography. These data suggest that DJ-1 works in parallel to the PINK1/parkin pathway to maintain mitochondrial function in the presence of an oxidative environment...
  44. pmc Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair
    Maria Victoria Botuyan
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Cell 127:1361-73. 2006
    ..This study reveals an evolutionarily conserved molecular mechanism of targeting DNA repair proteins to DSBs by direct recognition of H4-K20me2...
  45. ncbi Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
    J P Hugot
    Fondation Jean Dausset CEPH, 27 rue J Dodu 75010 Paris, France
    Nature 411:599-603. 2001
    ....
  46. ncbi Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks
    Yentram Huyen
    Wistar Institute, Philadelphia, Pennsylvania 19104 4268, USA
    Nature 432:406-11. 2004
    ..Because methylation of histone H3 Lys 79 was unaltered in response to DNA damage, we propose that 53BP1 senses DSBs indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site...
  47. ncbi Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation
    Fuminori Tokunaga
    Department of Biophysics and Biochemistry, Graduate School of Medicine and Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565 0871, Japan
    Nat Cell Biol 11:123-32. 2009
    ..These results indicate that LUBAC is involved in the physiological regulation of the canonical NF-kappaB activation pathway through linear polyubiquitylation of NEMO...
  48. ncbi Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting
    Lars Jakobsson
    Vascular Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Nat Cell Biol 12:943-53. 2010
    ..The regular exchange of the leading tip cell raises novel implications for the concept of guided angiogenic sprouting...
  49. ncbi The SYK tyrosine kinase: a crucial player in diverse biological functions
    Attila Mocsai
    Department of Physiology, Semmelweis University School of Medicine, 1094 Budapest, Hungary
    Nat Rev Immunol 10:387-402. 2010
    ..Moreover, SYK has a crucial role in autoimmune diseases and haematological malignancies. This Review summarizes our current understanding of the diverse functions of SYK and how this is being translated for therapeutic purposes...
  50. pmc Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions
    Peter J Cook
    Howard Hughes Medical Institute School of Medicine, University of California, San Diego, California 92037, USA
    Nature 458:591-6. 2009
    ....
  51. ncbi Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis
    Irene Noguera-Troise
    Regeneron Research Laboratories, 777 Old Saw Mill River Road, Tarrytown, New York 10591, USA
    Nature 444:1032-7. 2006
    ....
  52. 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...
  53. ncbi A family of cytokine-inducible inhibitors of signalling
    R Starr
    The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia
    Nature 387:917-21. 1997
    ..Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction...
  54. ncbi Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins
    A M Verhagen
    The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia
    Cell 102:43-53. 2000
    ..As transfection of cells with DIABLO was able to counter the protection afforded by MIHA against UV irradiation, DIABLO may promote apoptosis by binding to IAPs and preventing them from inhibiting caspases...
  55. pmc SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia
    Helen B Pearson
    Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    J Clin Invest 121:4257-67. 2011
    ..These data suggest that the polarity network could provide a new avenue for therapeutic intervention...
  56. pmc The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization
    Rosa M Canet-Aviles
    Laboratory of Neurogenetics, National Institute on Aging, 9000 Rockville Pike, Bethesda, MD 20892 1589, USA
    Proc Natl Acad Sci U S A 101:9103-8. 2004
    ..We suggest that DJ-1 protects against neuronal death, and that this is signaled by acidification of the key cysteine residue, C106...
  57. ncbi Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
    Olaf Gross
    III Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Str 22, 81675 Munich, Germany
    Nature 459:433-6. 2009
    ..Thus, our results demonstrate the molecular basis for IL-1beta production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo...
  58. ncbi Hypothalamic regulation of sleep and circadian rhythms
    Clifford B Saper
    Department of Neurology and Program in Neuroscience, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, USA
    Nature 437:1257-63. 2005
    ..These findings explain how various drugs affect sleep and wakefulness, and provide the basis for a wide range of environmental influences to shape wake-sleep cycles into the optimal pattern for survival...
  59. ncbi Human hypertension caused by mutations in WNK kinases
    F H Wilson
    Howard Hughes Medical Institute Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06510 USA
    Science 293:1107-12. 2001
    ..WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs...
  60. ncbi The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks
    Klara Acs
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    Nat Struct Mol Biol 18:1345-50. 2011
    ..1 or CDC-48.2, or cofactors UFD-1 or NPL-4, are highly sensitive to ionizing radiation. Our data suggest that human RNF8 and RNF168 promote VCP-mediated displacement of L3MBTL1 to unmask 53BP1 chromatin binding sites...
  61. ncbi RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor
    L M McLatchie
    Receptor Systems and Cell Biology Units, Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK
    Nature 393:333-9. 1998
    ..RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CGRP receptor. RAMP2-transported receptors are core-glycosylated and are adrenomedullin receptors...
  62. ncbi The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis
    Kieran F Harvey
    Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA
    Cell 114:457-67. 2003
    ..Hpo, Sav, and Wts interact physically and functionally, and regulate DIAP1 levels, likely by Hpo-mediated phosphorylation and subsequent degradation. Thus, Hpo links Sav and Wts to a key regulator of apoptosis...
  63. ncbi Two histone marks establish the inner centromere and chromosome bi-orientation
    Yuya Yamagishi
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113 0032, Japan
    Science 330:239-43. 2010
    ..Haspin colocalizes with cohesin by associating with Pds5, whereas Bub1 localizes at kinetochores. Thus, the inner centromere is defined by intersection of two histone kinases...
  64. pmc Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis
    Fangwei Wang
    Division of Rheumatology, Immunology, and Allergy, Brigham and Women s Hospital, Harvard Medical School, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA
    Science 330:231-5. 2010
    ..Therefore, H3T3ph generated by Haspin positions the CPC at centromeres to regulate selected targets of Aurora B during mitosis...
  65. ncbi Arousal and reward: a dichotomy in orexin function
    Glenda C Harris
    Department of Psychiatry, University of Pennsylvania, Translational Research Labs 3403, 125 South 31st Street, Philadelphia, PA 19104, USA
    Trends Neurosci 29:571-7. 2006
    ..Evidence also indicates roles for lateral hypothalamus orexin neurons and ventral tegmental orexin receptors in reward-based learning and memory...
  66. pmc MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites
    Huadong Pei
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    Nature 470:124-8. 2011
    ..Thus, we propose that a pathway involving γH2AX-MDC1-MMSET regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates 53BP1 recruitment...
  67. ncbi Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation
    Claire Bertet
    Laboratoire de Genetique et de Physiologie du Developpement, Institut de Biologie du Developpement de Marseille, CNRS Inserm Université de la Méditerranée, Campus de Luminy, Case 907, 13288 Marseille Cedex 9, France
    Nature 429:667-71. 2004
    ..This simple cellular mechanism provides a general model for polarized morphogenesis in epithelial organs...
  68. ncbi From promiscuity to precision: protein phosphatases get a makeover
    David M Virshup
    Program in Cancer and Stem Cell Biology, Duke NUS Graduate Medical School Singapore, Singapore, Republic of Singapore
    Mol Cell 33:537-45. 2009
    ..As recent publications illustrate, these regulatory subunits confer specificity, selectivity, localization, and regulation on these important enzymes...
  69. ncbi Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation
    R M Chemelli
    Howard Hughes Medical Institute, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75235 9050, USA
    Cell 98:437-51. 1999
    ..We propose that orexin regulates sleep/wakefulness states, and that orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation...
  70. ncbi The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness
    Takeshi Sakurai
    Department of Pharmacology, Institute of Basic Medical Science, University of Tsukuba, Ibaraki 305 8575, Japan
    Nat Rev Neurosci 8:171-81. 2007
    ..The orexin (hypocretin) system regulates sleep and wakefulness through interactions with systems that regulate emotion, reward and energy homeostasis...
  71. pmc Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded
    Jianzhong Yu
    Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA
    Dev Cell 18:288-99. 2010
    ..These results shed light on the mechanism of Ex and Mer function and implicate Kibra as a potential tumor suppressor with relevance to neurofibromatosis...
  72. ncbi RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems
    Koichi Kobayashi
    Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 416:194-9. 2002
    ..Rip2 is therefore a signal transducer and integrator of signals for both the innate and adaptive immune systems...
  73. pmc Modulation of intracellular ROS levels by TIGAR controls autophagy
    Karim Bensaad
    The Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow, UK
    EMBO J 28:3015-26. 2009
    ....
  74. pmc Genomewide association study for susceptibility genes contributing to familial Parkinson disease
    Nathan Pankratz
    Indiana University School of Medicine, Health Information and Translational Sciences Building, Indianapolis, IN 46202 3002, USA
    Hum Genet 124:593-605. 2009
    ..8 x 10(-6); additive model: p = 4.8 x 10(-5)). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility...
  75. pmc Afferents to the orexin neurons of the rat brain
    Kyoko Yoshida
    Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    J Comp Neurol 494:845-61. 2006
    ..These observations suggest that the orexin neurons may integrate a variety of interoceptive and homeostatic signals to increase behavioral arousal in response to hunger, stress, circadian signals, and autonomic challenges...
  76. ncbi TNF-alpha induces two distinct caspase-8 activation pathways
    Lai Wang
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell 133:693-703. 2008
    ..These findings revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP...
  77. pmc Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL 33136, USA
    Science 327:1135-9. 2010
    ..These findings suggest mechanism of A20 action in the inhibition of inflammatory signaling pathways...
  78. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
    ..We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations...
  79. pmc 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility
    Nadya Dimitrova
    The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    Nature 456:524-8. 2008
    ....
  80. ncbi Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth
    Tsutomu Ohta
    Center for Medical Genomics, National Cancer Center Research Institute, Tokyo 104 0045, Japan
    Cancer Res 68:1303-9. 2008
    ..Thus, inhibition of NRF2 may provide new therapeutic approaches in lung cancers with activation of Nrf2...
  81. ncbi Neural substrates of awakening probed with optogenetic control of hypocretin neurons
    Antoine R Adamantidis
    Department of Psychiatry and Behavioral Sciences, Stanford University, 701B Welch Road, Palo Alto, California 94304, USA
    Nature 450:420-4. 2007
    ..This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology...
  82. ncbi The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology
    Lars Vereecke
    Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent B 9052, Belgium
    Trends Immunol 30:383-91. 2009
    ..These findings further illustrate the importance of A20 in the resolution of inflammation and the prevention of human disease...
  83. ncbi Tumor suppressor LATS1 is a negative regulator of oncogene YAP
    Yawei Hao
    Department of Pathology and Molecular Medicine, Queen s University, Kingston, Ontario K7L 3N6, Canada
    J Biol Chem 283:5496-509. 2008
    ..These research findings will have profound impacts on our understanding of the molecular mechanism of the LATS tumor suppressor and the emerging Hippo-LATS/Warts pathway...
  84. ncbi Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis
    John Ridgway
    Tumor Biology and Angiogenesis, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 444:1083-7. 2006
    ..Therefore, targeting Dll4 might represent a broadly efficacious and well-tolerated approach for the treatment of solid tumours...
  85. ncbi Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer
    Balasundaram Padmanabhan
    RIKEN Genomic Sciences Center, Tsurumi, Yokohama 230 0045, Japan
    Mol Cell 21:689-700. 2006
    ..These results provide a structural basis for the loss of Keap1 function and gain of Nrf2 function...
  86. pmc ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy
    Ian G Ganley
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Biol Chem 284:12297-305. 2009
    ..ATG13.FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis...
  87. pmc Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization
    S V Costes
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Mutat Res 704:78-87. 2010
    ..Thus, heritable persistent RIF spanning over tens of Mbp may reflect persistent changes in the transcriptome of a large progeny of cells. Such model opens the door to a "non-DNA-centric view" of radiation-induced phenotypes...
  88. pmc Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways
    I Rappold
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Cell Biol 153:613-20. 2001
    ..Third, 53BP1 is readily phosphorylated by ATM in vitro. Taken together, these results suggest that 53BP1 is an ATM substrate that is involved early in the DNA damage-signaling pathways in mammalian cells...
  89. ncbi Frequent inactivation of A20 in B-cell lymphomas
    Motohiro Kato
    Cancer Genomics Project, Department of Pediatrics, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Nature 459:712-6. 2009
    ....
  90. ncbi MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells
    Tao Li
    Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University, China
    Biochem Biophys Res Commun 383:280-5. 2009
    ..Gene therapy using miR-21 inhibition strategy may therefore be useful as a prostate cancer therapy...
  91. ncbi Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis
    Xue Li
    Howard Hughes Medical Institute, School and Department of Medicine, UCSD, 9500 Gilman Drive, Room 345, La Jolla, California 92093 0648, USA
    Nature 426:247-54. 2003
    ....
  92. pmc Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
    Indra Adrianto
    Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
    Nat Genet 43:253-8. 2011
    ..These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE...
  93. ncbi The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis
    Rui Benedito
    Cancer Research UK London Research Institute, Vascular Development Laboratory, London, UK
    Cell 137:1124-35. 2009
    ....
  94. pmc Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development
    Nicholas W Gale
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA
    Proc Natl Acad Sci U S A 101:15949-54. 2004
    ..In summary, Dll4 appears to be a major trigger of Notch receptor activities previously implicated in arterial and vascular development, and it may represent a new opportunity for pro- and anti-angiogenic therapies...
  95. pmc Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer
    Anju Singh
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
    PLoS Med 3:e420. 2006
    ..Increased expression of cellular antioxidants and xenobiotic detoxification enzymes has been implicated in resistance of tumor cells against chemotherapeutic drugs...
  96. ncbi The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control
    I Garkavtsev
    Department of Medical Biochemistry and Southern Alberta Cancer Research Center, University of Calgary, Canada
    Nature 391:295-8. 1998
    ..These results indicate that p33ING1 is a component of the p53 signalling pathway that cooperates with p53 in the negative regulation of cell proliferation by modulating p53-dependent transcriptional activation...
  97. ncbi Cryopyrin activates the inflammasome in response to toxins and ATP
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 440:228-32. 2006
    ..Therefore, cryopyrin is essential for inflammasome activation in response to signalling pathways triggered specifically by ATP, nigericin, maitotoxin, S. aureus or L. monocytogenes...
  98. ncbi Pseudo-DNA damage response in senescent cells
    Tatyana V Pospelova
    Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia
    Cell Cycle 8:4112-8. 2009
    ..Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells...
  99. ncbi Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans)
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 9:683-8. 2010
    ..Therefore in humans the effect of CR may be somewhat blunted. Still how much does CR extend human lifespan? And could this extension be surpassed by gerosuppressants such as rapamycin?..
  100. ncbi Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts
    A Wodarz
    Institut fur Genetik, Heinrich Heine Universitat Dusseldorf, Germany
    Nature 402:544-7. 1999
    ..As Bazooka is also responsible for the maintenance of apical-basal polarity in epithelial tissues, it may be the missing link between epithelial polarity and neuroblast polarity...
  101. pmc Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection
    Matthew J Robinson
    Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, London WC2A 3PX, England, UK
    J Exp Med 206:2037-51. 2009
    ..Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk-CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection...

Research Grants62

  1. SIGNALING THROUGH RHO GTP/GDP EXCHANGE FACTORS
    Philip B Wedegaertner; Fiscal Year: 2013
    ..The research in this application will provide new knowledge about the functions of RhoGEFs and thus better define how the RhoGEFs can be therapeutically inhibited in disease without affecting their critical normal functions. ..
  2. L1CAM Adhesion and Signaling Pathways in C. elegans
    Lihsia Chen; Fiscal Year: 2012
    ..elegans will define mechanisms that control L1CAM function and provide insights into the physiological mechanism of these disorders, which will help lead to therapeutic development. ..
  3. STRESS SIGNALING PATHWAYS LINKING ENDOTHELIAL INJURY TO GRAFT ARTERIOSCLEROSIS
    Wang Min; Fiscal Year: 2013
    ..If successful, this study will provide therapeutic strategies by modulating these two molecules in ECs to reduce GA incidence or delay GA progression. ..
  4. Cellular Mechanisms in Animal Models of Depression
    John R Traynor; Fiscal Year: 2011
    ..Our aim is to identify novel targets for the development of agents to treat depressive illness. ..
  5. Effects of diacylglycerol kinase zeta deficiency on CD8+ T cell function
    Matthew J Riese; Fiscal Year: 2013
    ..We have found a new target for treating cancer, dgk-zeta, which awakens the immune system in mice, preventing cancer growth. This grant will figure out exactly how dgk-zeta works in a type of T cell known to attack cancer cells. ..
  6. Mechanisms of Integrin-Linked Transduction by Recombinant Adeno-Associated Virus
    PAUL M KAMINSKY; Fiscal Year: 2012
    ..abstract_text> ..
  7. Synthesis and Evaluation of Functionally Biased Opioid Analgesics
    Laura M Bohn; Fiscal Year: 2013
    ..The information garnered from this proposal will prove useful in the future development of clinical pain relievers with limited side effects. ..
  8. Roundabout4 signaling in endothelial cells
    Ramani Ramchandran; Fiscal Year: 2012
    ..Each mechanistic step is a putative target and drugs targeting these steps will benefit diseases characterized by excessive angiogenesis and vascular leakage. ..
  9. Pathophysiological role of prorenin in CKD
    Alfred K Cheung; Fiscal Year: 2013
    ..This project perfectly aligns with the mission of the NIDDK to study and develop treatments for people with CKD and diabetes. ..
  10. Transcriptional control of FSH expression
    Daniel Bernard; Fiscal Year: 2007
    ..Given the critical importance of FSH for fertility in women, these results may aid in the design of novel contraceptives or may pinpoint causes of infertility that have thus far eluded our detection. ..
  11. Receptor Organization, SMAC Dynamics and membrane Lipids in Aging T Cells
    Abraham Kupfer; Fiscal Year: 2007
    ..If these declines could be arrested or reduced the large population of older Americans would be less susceptible to infection with profound social and economic consequences. [unreadable] [unreadable] [unreadable]..
  12. CAAX Processing Enzymes as Anticancer Targets
    Stephen Young; Fiscal Year: 2005
    ..Using these mice, we will define the impact of defective CAAX processing on the development, progression, and lethality of Ras-induced myeloproliferative disease. ..
  13. REGULATION OF ANGIOGENESIS BY THROMBOSPONDIN
    William Frazier; Fiscal Year: 2004
    ..The TSP/CD36 system provides a normally functioning entre into the control of angiogenesis in which the ligand and receptor are well defined and whose mechanism will be elucidated as indicated above. ..
  14. Regulation of Endothelial Cell Function in Angiogenesis
    KATHERINE HAJJAR; Fiscal Year: 2005
    ..abstract_text> ..
  15. MECHANISMS OF TNF/CYTOKINE ACTIONS
    Jan Vilcek; Fiscal Year: 2002
    ..These studies will help to understand signaling pathways activated by TNF and will contribute to the design of methods for the inhibition of undesirable side effects of TNF in pathological conditions. ..
  16. Investigation of a sodium channel signaling complex
    TIGWA DAVIS; Fiscal Year: 2004
    ..abstract_text> ..
  17. SIGNAL TRANSDUCTION MECHANISMS IN BACTERIAL CHEMOTAXIS
    Richard Stewart; Fiscal Year: 2009
    ..Our results will help to define general concepts about regulation and clustering of receptor-kinase complexes. ..
  18. Molecular Crosstalk in Intracellular Signaling Netoworks
    JASON HAUGH; Fiscal Year: 2006
    ..Finally, for conditions found to perturb the signaling network, the corresponding effects on cell proliferation and survival will be assessed. ..
  19. Squamous Cell Carcinoma and Topographic Cuing
    Christopher Murphy; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  20. Membrane Targeting of G Proteins
    Philip Wedegaertner; Fiscal Year: 2007
    ..abstract_text> ..
  21. Estrogen Modulates Dopamine Signaling
    JILL SHARIFI; Fiscal Year: 2005
    ..Data collected will provide important evidence for estrogen's role in the modulation of the nucleus accumbens reward system and drugs of abuse. ..
  22. NEGATIVE REGULATORS OF MYELOPOIESIS
    Barbara Hoffman; Fiscal Year: 2009
    ..This knowledge should provide novel tools for designing drugs to promote differentiation and/or apoptosis of leukemic cells. ..
  23. Aging and IGF-I in Cartilage
    RICHARD LOESER; Fiscal Year: 2009
    ..The results from this project should continue to provide new information needed to establish the basic cellular and molecular mechanisms which link aging to the development of OA in humans. ..
  24. Gadd 45 in the Response of Hematopoietic Cells to Stress
    Dan A Liebermann; Fiscal Year: 2010
    ....
  25. INTERLEUKIN 15 RECEPTOR AND LYMPHOID HOMEOSTASIS
    AVERIL I MA; Fiscal Year: 2010
    ..Future attempts to either enhance antiviral vaccine effectiveness or to suppress persistent inflammation in autoimmune conditions may benefit greatly from the mechanistic insights we are gaining into IL-15 biology. ..
  26. Circadian Regulation of Olfaction
    STUART DRYER; Fiscal Year: 2004
    ..abstract_text> ..
  27. Regulation of cyclin-dependent kinase inhibitor p27 in cancer
    Mong Hong Lee; Fiscal Year: 2008
    ..abstract_text> ..
  28. HYPOTHALAMIC HYPOCRETIN PATHWAYS MODULATING FEEDING
    CATHERINE KOTZ; Fiscal Year: 2004
    ....
  29. Hsal 2, A Novel Homeobox Gene in Hematopoiesis
    Li Chai; Fiscal Year: 2007
    ..In addition, a further objective of this proposal is to serve as a vehicle for the development of the candidate into an independent and productive investigator in the area of hematopoiesis and leukemogenesis. ..
  30. AACR-TREC-NIH Think Tank Conference: Energy Balance and Cancer; Mechanisms and Me
    Nathan Berger; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  31. CDC 42 BIM AND THE OSTEOCLAST
    Steven L Teitelbaum; Fiscal Year: 2010
    ..abstract_text> ..
  32. Regulation of T Cell and Mast Cell Function by DGKzeta
    Gary A Koretzky; Fiscal Year: 2010
    ..We anticipate that this work will shed additional light on the complex regulation of T cell and mast cell function and will hopefully suggest novel approaches to modulate activity of these cell types. ..
  33. CYCLOSPORINE, TGF BETA1, AND IMMUNOSUPPRESSION
    Manikkam Suthanthiran; Fiscal Year: 2002
    ....
  34. STRUCTURE/FUNCTION OF SH2 DOMAIN OF SLP 76
    Gary Koretzky; Fiscal Year: 2002
    ..Collectively, we hope these studies will provide insights into the complex regulation of signaling by SLP-76 and LAT in T cell development and activation. ..
  35. PHOSPHORYLATION OF LUPUS AUTOANTIGENS IN APOPTOSIS
    PAUL UTZ; Fiscal Year: 2002
    ....
  36. The hypocretins and alcohol dependence
    Luis de Lecea; Fiscal Year: 2003
    ..The development of these mouse models will generate invaluable tools to assess the role of the hypocretins on drug abuse, and may help to design better treatments for sleep disorders associated with alcoholism. ..
  37. Gender Differences in Dopamine Function after TBI
    Amy Wagner; Fiscal Year: 2003
    ....
  38. FAT MEDIATED INSULIN SECRETION AND DIABETES IN ELDERLY
    Guenther Boden; Fiscal Year: 2003
    ..We hope that this project will help to better understand the mechanisms by which obesity contributes to the development of NIDDM. ..
  39. Autoantigen Arrays to Select Vaccines for Model of PBC
    PAUL UTZ; Fiscal Year: 2003
    ..Successful treatment of EAC using plasmids encoding prominent autoantigens may herald an era of customized, antigen- or tissue- specific tolerizing therapy in humans. ..
  40. CELLULAR & ONCOGENIC CONTROL OF INTERFERON INDUCED GENES
    NANCY REICH; Fiscal Year: 2004
    ..These studies will benefit our understanding of critical cellular responses to stress. ..
  41. Measuring Striatal Neurotransmission in Behaving Rats after Experimental TBI
    Amy Wagner; Fiscal Year: 2008
    ..The overarching goal is to gain insight into potential mechanisms of action and efficacy of these interventions on cognition and recovery for the clinical population with TBI. [unreadable] [unreadable] [unreadable]..
  42. IL-15Ra and NK Cell Function
    Averil Ma; Fiscal Year: 2008
    ..These experiments should reveal novel insights into which cells use IL-15Ra to supports NK cells in vivo, and how IL-15Ra performs its unusual molecular function. ..
  43. Shuttling of Peroxisomal Targeting Sequence Receptors
    Suresh Subramani; Fiscal Year: 2006
    ..What peroxins are necessary for the shuttling of Pex5p into and out of peroxisomes?5. Does Pex7p cycle into and out of the peroxisome matrix in yeast and in mammals? If so, what is the mechanism by which Pex7p shuttles? ..
  44. Mechanism of Meclp in the Checkpoint Response
    GEORGE BRUSH; Fiscal Year: 2006
    ..It is expected that these studies will provide significant insight into the molecular mechanisms underlying maintenance of the non-cancerous state under genotoxic conditions. ..
  45. NOVEL SUBSTRATES OF THE TCR KINASE
    Gary Koretzky; Fiscal Year: 2005
    ..We anticipate that collectively these studies will provide new insights into how this protein (and by extension other proteins with similar functional domains) may function in the regulation of cellular activation. ..
  46. Lymphocyte Activation and Signaling
    Gary Koretzky; Fiscal Year: 2006
    ..abstract_text> ..
  47. Voluntary Exercise Therapy after Traumatic Brain Injury
    GRACE GRIESBACH; Fiscal Year: 2006
    ..In order to address these specific aims, I will utilize the lateral fluid-percussion injury model in rats and voluntary running wheel exposure. Protein, gene, histological and behavioral studies will be conducted. ..
  48. Protection by Induction of Ubiquitin-Proteasome Systems
    Thomas Kensler; Fiscal Year: 2005
    ....
  49. Dopamine Function in TBI--Therapeutic Intervention
    Amy Wagner; Fiscal Year: 2005
    ..The Departments of Physical Medicine and Rehabilitation, Neurosurgery, Anesthesia/Critical Care Medicine, and Safar Center for Resuscitation Research provide the environment for this study of experimental and clinical brain injury. ..
  50. Synaptic Alterations in the Cerebral Cortex during Aging
    A Cuello; Fiscal Year: 2005
    ..abstract_text> ..
  51. Phase III Colon Cancer Prevention Trial
    Frank Meyskens; Fiscal Year: 2006
    ..The overall goal of our work is to develop safe combinations of chemoprevention agents that can be used in the practice setting and complement current surveillance efforts. ..
  52. PanAmerican Society for Pigment Cell Research (PASPCR)
    Frank Meyskens; Fiscal Year: 2004
    ..abstract_text> ..
  53. Crosstalk between oncoprotein Ski and TGF-B signaling
    Yin Sun; Fiscal Year: 2008
    ..abstract_text> ..
  54. CONTROL OF MATRIX PROTEOLYSIS BY INTEGRIN A3B1 IN SKIN
    C DiPersio; Fiscal Year: 2005
    ....
  55. Chemopreventive Efficacy of Broccoli Sprouts in Humans
    Thomas Kensler; Fiscal Year: 2004
    ..abstract_text> ..
  56. Molecular Control of cGMP Signaling by PKGs and PDEs
    Jackie Corbin; Fiscal Year: 2007
    ..A thorough physical and biochemical characterization of PDE11 will be carded out, and the likelihood of regulation of this enzyme by ligand binding to its GAF domains or by enzyme phosphorylation will be explored. ..
  57. Analysis of fringe-dependent cell-signaling
    Kenneth Irvine; Fiscal Year: 2004
    ....
  58. Perilipiin and Lipolysis
    Andrew Greenberg; Fiscal Year: 2007
    ..These data will be directed to the prevention and treatment of diabetes, hyperlipidemia and other obesity - associated disorders. ..
  59. Multiplex Autoantibody Profiling in SLE
    PAUL UTZ; Fiscal Year: 2007
    ..Moreover, further development of protein microarray technology will have broad applications to the fields of immunology, functional genomics, and proteomics. ..
  60. Lysate Arrays for Studying the Diabetes Proteome
    PAUL UTZ; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  61. SIGNAL TRANSDUCTION IN THE IMMUNE SYSTEM-FASEB CONF.
    Gary Koretzky; Fiscal Year: 2005
    ..3) To continue a biannual forum for investigators interested in a comprehensive focus on signaling events in the immune system. ..