signal transduction

Summary

Summary: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

Top Publications

  1. doi Hallmarks of cancer: the next generation
    Douglas Hanahan
    The Swiss Institute for Experimental Cancer Research ISREC, School of Life Sciences, EPFL, Lausanne CH 1015, Switzerland
    Cell 144:646-74. 2011
  2. pmc mTOR signaling in growth control and disease
    Mathieu Laplante
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell 149:274-93. 2012
  3. ncbi The biology of VEGF and its receptors
    Napoleone Ferrara
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Med 9:669-76. 2003
  4. pmc An integrated genomic analysis of human glioblastoma multiforme
    D Williams Parsons
    Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1807-12. 2008
  5. pmc Reactome: a database of reactions, pathways and biological processes
    David Croft
    European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
    Nucleic Acids Res 39:D691-7. 2011
  6. pmc TGFbeta in Cancer
    Joan Massague
    Cancer Biology and Genetics Program, and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 134:215-30. 2008
  7. ncbi Integrins: bidirectional, allosteric signaling machines
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 110:673-87. 2002
  8. pmc Understanding the Warburg effect: the metabolic requirements of cell proliferation
    Matthew G Vander Heiden
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 324:1029-33. 2009
  9. ncbi TOR signaling in growth and metabolism
    Stephan Wullschleger
    Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Cell 124:471-84. 2006
  10. ncbi Free radicals in the physiological control of cell function
    Wulf Dröge
    Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Physiol Rev 82:47-95. 2002

Detail Information

Publications332 found, 100 shown here

  1. doi Hallmarks of cancer: the next generation
    Douglas Hanahan
    The Swiss Institute for Experimental Cancer Research ISREC, School of Life Sciences, EPFL, Lausanne CH 1015, Switzerland
    Cell 144:646-74. 2011
    ..Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer...
  2. pmc mTOR signaling in growth control and disease
    Mathieu Laplante
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell 149:274-93. 2012
    ..Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation...
  3. ncbi The biology of VEGF and its receptors
    Napoleone Ferrara
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Med 9:669-76. 2003
    ..VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration...
  4. pmc An integrated genomic analysis of human glioblastoma multiforme
    D Williams Parsons
    Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1807-12. 2008
    ..These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs...
  5. pmc Reactome: a database of reactions, pathways and biological processes
    David Croft
    European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
    Nucleic Acids Res 39:D691-7. 2011
    ..The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome framework for chicken, Drosophila and rice...
  6. pmc TGFbeta in Cancer
    Joan Massague
    Cancer Biology and Genetics Program, and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 134:215-30. 2008
    ..The mechanistic basis and clinical relevance of TGFbeta's role in cancer is becoming increasingly clear, paving the way for a better understanding of the complexity and therapeutic potential of this pathway...
  7. ncbi Integrins: bidirectional, allosteric signaling machines
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 110:673-87. 2002
    ..their extracellular ligand binding adhesion sites and their cytoplasmic domains, which link to the cytoskeleton and to signal transduction pathways. Long-range conformational changes couple these functions via allosteric equilibria.
  8. pmc Understanding the Warburg effect: the metabolic requirements of cell proliferation
    Matthew G Vander Heiden
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 324:1029-33. 2009
    ..A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer...
  9. 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...
  10. ncbi Free radicals in the physiological control of cell function
    Wulf Dröge
    Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Physiol Rev 82:47-95. 2002
    ..tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes...
  11. ncbi BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks
    Steven Maere
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology VIB, Ghent University, Technologiepark 927, B 9052, Ghent, Belgium
    Bioinformatics 21:3448-9. 2005
    ....
  12. doi The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
    Taro Kawai
    Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
    Nat Immunol 11:373-84. 2010
    ..Here we describe the recent advances that have been made by research into the role of TLR biology in host defense and disease...
  13. pmc Core signaling pathways in human pancreatic cancers revealed by global genomic analyses
    Sian Jones
    Sol Goldman Pancreatic Cancer Research Center, Ludwig Center and Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1801-6. 2008
    ..Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis...
  14. doi Shared principles in NF-kappaB signaling
    Matthew S Hayden
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 132:344-62. 2008
    ..Here, we attempt to synthesize some of the basic principles that have emerged from studies of NF-kappaB, and we aim to generate a more unified view of NF-kappaB regulation...
  15. pmc NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses
    Konstantin D Taganov
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 103:12481-6. 2006
    ....
  16. doi Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
    Taro Kawai
    Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
    Immunity 34:637-50. 2011
    ..In this review, we will focus on the role played by TLRs in mounting protective immune responses against infection and their crosstalk with other PRRs with respect to pathogen recognition...
  17. pmc The mutational landscape of head and neck squamous cell carcinoma
    Nicolas Stransky
    The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Science 333:1157-60. 2011
    ..More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms...
  18. ncbi Stem cells, cancer, and cancer stem cells
    T Reya
    Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Palo Alto, California 94305, USA
    Nature 414:105-11. 2001
    ....
  19. 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...
  20. ncbi Cell migration: integrating signals from front to back
    Anne J Ridley
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London W1W 7BS, UK
    Science 302:1704-9. 2003
    ....
  21. ncbi A synaptic model of memory: long-term potentiation in the hippocampus
    T V Bliss
    Division of Neurophysiology and Neuropharmacology, National Institute of Medical Research, Mill Hill, London, UK
    Nature 361:31-9. 1993
    ....
  22. doi The unfolded protein response: from stress pathway to homeostatic regulation
    Peter Walter
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA
    Science 334:1081-6. 2011
    ..The ER responds to the burden of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways, collectively termed the unfolded protein response (UPR)...
  23. ncbi MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Science 316:1039-43. 2007
    ..Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well...
  24. ncbi Oxidants, oxidative stress and the biology of ageing
    T Finkel
    Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, Maryland 20892 1622, USA
    Nature 408:239-47. 2000
    ..Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span...
  25. pmc Integrative genomic profiling of human prostate cancer
    Barry S Taylor
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Cancer Cell 18:11-22. 2010
    ..The genomic and clinical outcome data from these patients are now made available as a public resource...
  26. ncbi Rho GTPases in cell biology
    Sandrine Etienne-Manneville
    MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, University College London, Gower Street, London WC1E 6BT, UK
    Nature 420:629-35. 2002
    Rho GTPases are molecular switches that control a wide variety of signal transduction pathways in all eukaryotic cells...
  27. ncbi Free radicals and antioxidants in normal physiological functions and human disease
    Marian Valko
    Faculty of Chemical and Food Technology, Slovak Technical University, SK 812 37 Bratislava, Slovakia
    Int J Biochem Cell Biol 39:44-84. 2007
    ..Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury...
  28. pmc Inflammation and insulin resistance
    Steven E Shoelson
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 116:1793-801. 2006
    ....
  29. ncbi Cancer genes and the pathways they control
    Bert Vogelstein
    Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA
    Nat Med 10:789-99. 2004
    ..The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation...
  30. ncbi Hypoxia--a key regulatory factor in tumour growth
    Adrian L Harris
    Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
    Nat Rev Cancer 2:38-47. 2002
    ..Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting...
  31. doi Rab GTPases as coordinators of vesicle traffic
    Harald Stenmark
    Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Montebello, N 0310 Oslo, Norway
    Nat Rev Mol Cell Biol 10:513-25. 2009
    ..Functional impairments of Rab pathways are associated with diseases, such as immunodeficiencies, cancer and neurological disorders...
  32. ncbi Mechanisms of TGF-beta signaling from cell membrane to the nucleus
    Yigong Shi
    Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA
    Cell 113:685-700. 2003
    ..This article reviews these latest advances and presents our current understanding on the mechanisms of TGF-beta signaling from cell membrane to the nucleus...
  33. ncbi Reactive oxygen species: metabolism, oxidative stress, and signal transduction
    Klaus Apel
    Institute of Plant Sciences, Swiss Federal Institute of Technology, Universitätstr 2, 8092 Zurich, Switzerland
    Annu Rev Plant Biol 55:373-99. 2004
    ..Considering recent ROS-induced genome-wide expression analyses, the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast...
  34. ncbi Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?
    Hector Peinado
    Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Madrid UAM, Instituto de Investigaciones Biomedicas Alberto Sols CSIC UAM, Arturo Duperier 4, 28029 Madrid, Spain
    Nat Rev Cancer 7:415-28. 2007
    ....
  35. pmc The DNA damage response: making it safe to play with knives
    Alberto Ciccia
    Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 40:179-204. 2010
    ..To respond to these threats, eukaryotes have evolved the DNA damage response (DDR). The DDR is a complex signal transduction pathway that has the ability to sense DNA damage and transduce this information to the cell to influence ..
  36. ncbi Self-eating and self-killing: crosstalk between autophagy and apoptosis
    M Chiara Maiuri
    INSERM, U848, F 94805 Villejuif, France
    Nat Rev Mol Cell Biol 8:741-52. 2007
    ..On a molecular level, this means that the apoptotic and autophagic response machineries share common pathways that either link or polarize the cellular responses...
  37. pmc AKT/PKB signaling: navigating downstream
    Brendan D Manning
    Department of Genetics and Complex Diseases, Harvard School of Public Health, SPH2 117, Boston, MA 02115, USA
    Cell 129:1261-74. 2007
    ..In addition, we discuss those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration...
  38. ncbi Pathogen recognition and innate immunity
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Cell 124:783-801. 2006
    ..New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity...
  39. ncbi Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene
    A Poltorak
    Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235 9050, USA
    Science 282:2085-8. 1998
    Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection...
  40. pmc Wnt/beta-catenin signaling: components, mechanisms, and diseases
    Bryan T MacDonald
    F M Kirby Neurobiology Center, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 17:9-26. 2009
    ..Finally, we highlight some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications...
  41. pmc Macrophage plasticity and polarization: in vivo veritas
    Antonio Sica
    Istituto Clinico Humanitas IRCCS, Rozzano, Italy
    J Clin Invest 122:787-95. 2012
    ..The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies...
  42. pmc Human Protein Reference Database--2009 update
    T S Keshava Prasad
    Institute of Bioinformatics, International Tech Park, Bangalore 560 066, India
    Nucleic Acids Res 37:D767-72. 2009
    ..Since the last update, more than 5500 new protein sequences have been added, making HPRD a comprehensive resource for studying the human proteome...
  43. ncbi Interleukin-10 and the interleukin-10 receptor
    K W Moore
    Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology Inc, Palo Alto, California 94304, USA
    Annu Rev Immunol 19:683-765. 2001
    ..This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease...
  44. ncbi Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA
    Science 306:457-61. 2004
    ..Pharmacologic manipulation of this pathway may offer novel opportunities for treating these common diseases...
  45. pmc The DNA-damage response in human biology and disease
    Stephen P Jackson
    The Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 461:1071-8. 2009
    ..Our improving understanding of DNA-damage responses is providing new avenues for disease management...
  46. doi Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis
    Jing Yang
    Department of Pharmacology and Pediatrics, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Dev Cell 14:818-29. 2008
    ..Studies in both fields are critical for our molecular understanding of cell migration and morphogenesis...
  47. ncbi A Toll-like receptor recognizes bacterial DNA
    H Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Suita
    Nature 408:740-5. 2000
    ..The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA...
  48. pmc mTOR: from growth signal integration to cancer, diabetes and ageing
    Roberto Zoncu
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Rev Mol Cell Biol 12:21-35. 2011
    ..In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing...
  49. ncbi Wnt signalling in stem cells and cancer
    Tannishtha Reya
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 434:843-50. 2005
    ....
  50. doi Regulation and function of NF-kappaB transcription factors in the immune system
    Sivakumar Vallabhapurapu
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, Cancer Center, University of California, San Diego, California 93093, USA
    Annu Rev Immunol 27:693-733. 2009
    ..This recent progress is covered in this review...
  51. ncbi A central role for JNK in obesity and insulin resistance
    Jiro Hirosumi
    Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA
    Nature 420:333-6. 2002
    ..Thus, JNK is a crucial mediator of obesity and insulin resistance and a potential target for therapeutics...
  52. pmc Mammalian autophagy: core molecular machinery and signaling regulation
    Zhifen Yang
    Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109 2216, USA
    Curr Opin Cell Biol 22:124-31. 2010
    ..Here we highlight the recent advances in identifying and understanding the core molecular machinery and signaling pathways that are involved in mammalian autophagy...
  53. ncbi Osteoclast differentiation and activation
    William J Boyle
    Protein Pathways, Inc, Woodland Hills, California 91367, USA
    Nature 423:337-42. 2003
    ..Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss...
  54. ncbi The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses
    Mitsutoshi Yoneyama
    Department of Tumor Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
    Nat Immunol 5:730-7. 2004
    ..Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes...
  55. pmc The canonical Notch signaling pathway: unfolding the activation mechanism
    Raphael Kopan
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell 137:216-33. 2009
    ..In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection...
  56. doi Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
    Kornelia Polyak
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:265-73. 2009
    ....
  57. ncbi MAPMAN: a user-driven tool to display genomics data sets onto diagrams of metabolic pathways and other biological processes
    Oliver Thimm
    Max Planck Institute for Molecular Plant Physiology, Golm, Germany
    Plant J 37:914-39. 2004
    ....
  58. ncbi IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
    Jochen Schmitz
    Schering Plough Biopharma Formerly DNAX Research, Inc, 901 California Avenue, Palo Alto, California 94304, USA
    Immunity 23:479-90. 2005
    ..In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs...
  59. pmc Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
    Science 313:1137-40. 2006
    ..Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes...
  60. doi Immunological and inflammatory functions of the interleukin-1 family
    Charles A Dinarello
    Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado 80045, USA
    Annu Rev Immunol 27:519-50. 2009
    ....
  61. ncbi Complex networks orchestrate epithelial-mesenchymal transitions
    Jean Paul Thiery
    Centre National de la Recherche Scientifique CNRS Unité Mixte Recherche UMR 144 and Institut Curie, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Nat Rev Mol Cell Biol 7:131-42. 2006
    ..Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression...
  62. pmc TLR4 links innate immunity and fatty acid-induced insulin resistance
    Hang Shi
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 116:3015-25. 2006
    ....
  63. doi Malignant gliomas in adults
    Patrick Y Wen
    Division of Neuro Oncology, Department of Neurology, Dana Farber corrected Brigham and Women s Hospital, Boston, MA 02115, USA
    N Engl J Med 359:492-507. 2008
  64. doi Regulation of cancer cell metabolism
    Rob A Cairns
    The Campbell Family Cancer Research Institute, Toronto, ON M56 2M9, Canada
    Nat Rev Cancer 11:85-95. 2011
    ....
  65. doi Lipid rafts as a membrane-organizing principle
    Daniel Lingwood
    Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
    Science 327:46-50. 2010
    ..Here we review the evidence for how this principle combines the potential for sphingolipid-cholesterol self-assembly with protein specificity to selectively focus membrane bioactivity...
  66. pmc Reactome knowledgebase of human biological pathways and processes
    Lisa Matthews
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Nucleic Acids Res 37:D619-22. 2009
    ..Reactome's data content and software can all be freely used and redistributed under open source terms...
  67. ncbi Toll-like receptor signalling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Rev Immunol 4:499-511. 2004
  68. pmc Protective and pathogenic functions of macrophage subsets
    Peter J Murray
    Department of Infectious Diseases, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA
    Nat Rev Immunol 11:723-37. 2011
    ..Finally, we briefly discuss the characterization of macrophage heterogeneity in humans...
  69. ncbi Brown adipose tissue: function and physiological significance
    Barbara Cannon
    The Wenner Gren Institute, The Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden
    Physiol Rev 84:277-359. 2004
    ....
  70. pmc Extending healthy life span--from yeast to humans
    Luigi Fontana
    Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 328:321-6. 2010
    ..We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects...
  71. ncbi Smad-dependent and Smad-independent pathways in TGF-beta family signalling
    Rik Derynck
    Department of Growth and Development, University of California at San Francisco, San Francisco, California 94143 0640, USA
    Nature 425:577-84. 2003
    ..Other signalling pathways further regulate Smad activation and function. In addition, TGF-beta receptors activate Smad-independent pathways that not only regulate Smad signalling, but also allow Smad-independent TGF-beta responses...
  72. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
    ..The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage ..
  73. pmc Autophagy and the integrated stress response
    Guido Kroemer
    INSERM, U848, 39 rue Calmette Desmoulins, 94805 Villejuif, France
    Mol Cell 40:280-93. 2010
    ..Thus, autophagy is a cell biological process that is a central component of the integrated stress response...
  74. doi The genetics of ageing
    Cynthia J Kenyon
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA
    Nature 464:504-12. 2010
    ..Which genes can extend lifespan? Can we augment their activities and live even longer? After centuries of wistful poetry and wild imagination, we are now getting answers, often unexpected ones, to these fundamental questions...
  75. ncbi Tumour stem cells and drug resistance
    Michael Dean
    Laboratory of Genomic Diversity, National Cancer Institute Frederick, Frederick, Maryland 21702, USA
    Nat Rev Cancer 5:275-84. 2005
    ..Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies...
  76. pmc TGFβ signalling in context
    Joan Massague
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Rev Mol Cell Biol 13:616-30. 2012
    ..However, an old mystery has endured: how does the context determine the cellular response to TGFβ? Solving this question is key to understanding TGFβ biology and its many malfunctions. Recent progress is pointing at answers...
  77. pmc Cell signaling by receptor tyrosine kinases
    Mark A Lemmon
    Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Cell 141:1117-34. 2010
    ..Much remains to be learned, however, about the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses...
  78. ncbi Signal integration in the endoplasmic reticulum unfolded protein response
    David Ron
    The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Nat Rev Mol Cell Biol 8:519-29. 2007
    ..ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways - cumulatively called the unfolded protein response (UPR)...
  79. ncbi Phosphoinositides in cell regulation and membrane dynamics
    Gilbert Di Paolo
    Department of Pathology and Cell Biology, The Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, New York 10032, USA
    Nature 443:651-7. 2006
    ..Their functions, besides classical signal transduction at the cell surface, include regulation of membrane traffic, the cytoskeleton, nuclear events and the ..
  80. pmc Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors
    Timothy R Wilson
    Research Oncology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 487:505-9. 2012
    ..These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases...
  81. 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...
  82. ncbi Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes
    Alberto Mantovani
    Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, I 20157 Milan, Italy
    Trends Immunol 23:549-55. 2002
    ..These functionally polarized cells, and similarly oriented or immature dendritic cells present in tumors, have a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression...
  83. ncbi Identification of c-MYC as a target of the APC pathway
    T C He
    Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
    Science 281:1509-12. 1998
    ..These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers...
  84. doi Integration of external signaling pathways with the core transcriptional network in embryonic stem cells
    Xi Chen
    Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672
    Cell 133:1106-17. 2008
    ..Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity...
  85. pmc The landscape of somatic copy-number alteration across human cancers
    Rameen Beroukhim
    Cancer Program and Medical and Population Genetics Group, The Broad Institute of M I T and Harvard, 7 Cambridge Center
    Nature 463:899-905. 2010
    ..Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types...
  86. pmc Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion
    Ravid Straussman
    The Eli and Edythe L Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 487:500-4. 2012
    ..More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance...
  87. pmc MicroRNA targets in Drosophila
    Anton J Enright
    Computational Biology Center, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Genome Biol 5:R1. 2003
    ..Application to the D. melanogaster, Drosophila pseudoobscura and Anopheles gambiae genomes identifies several hundred target genes potentially regulated by one or more known miRNAs...
  88. pmc An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis
    Matthew P R Berry
    Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Nature 466:973-7. 2010
    ..Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic...
  89. pmc PID: the Pathway Interaction Database
    Carl F Schaefer
    National Cancer Institute, Center for Biomedical Informatics and Information Technology, Rockville MD, USA
    Nucleic Acids Res 37:D674-9. 2009
    ..The database is updated with new pathway content every month and supplemented by specially commissioned articles on the practical uses of other relevant online tools...
  90. pmc Matrix crosslinking forces tumor progression by enhancing integrin signaling
    Kandice R Levental
    Department of Bioengineering and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cell 139:891-906. 2009
    ..These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy...
  91. pmc Integrins in cancer: biological implications and therapeutic opportunities
    Jay S Desgrosellier
    Department of Pathology, Moores University of California at San Diego Cancer Center, La Jolla, 92093 0803, United States
    Nat Rev Cancer 10:9-22. 2010
    ..These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment...
  92. ncbi The phosphatidylinositol 3-Kinase AKT pathway in human cancer
    Igor Vivanco
    Department of Medicine and Molecular Biology Institute, UCLA School of Medicine, 11 935 Factor Building, 10833 LeConte Avenue, Los Angeles, California 90095, USA
    Nat Rev Cancer 2:489-501. 2002
  93. ncbi Wnt/beta-catenin signaling in development and disease
    Hans Clevers
    Hubrecht Laboratory and Utrecht University, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands
    Cell 127:469-80. 2006
    A remarkable interdisciplinary effort has unraveled the WNT (Wingless and INT-1) signal transduction cascade over the last two decades. Wnt genes encode small secreted proteins that are found in all animal genomes...
  94. doi The biology of cancer: metabolic reprogramming fuels cell growth and proliferation
    Ralph J DeBerardinis
    Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Cell Metab 7:11-20. 2008
    ..We also consider regulation of these fluxes by cellular mediators of signal transduction and gene expression, including the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR system, hypoxia-inducible ..
  95. ncbi The Wnt signaling pathway in development and disease
    Catriona Y Logan
    Department of Developmental Biology, Beckman Center, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
    Annu Rev Cell Dev Biol 20:781-810. 2004
    ..The next few years are likely to see novel therapeutic reagents aimed at controlling Wnt signaling in order to alleviate these conditions...
  96. ncbi Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3
    Shunsuke Kimura
    Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    Autophagy 3:452-60. 2007
    ..This method will be of general utility for analysis of the autophagosome maturation process...
  97. doi Regulation of mammalian autophagy in physiology and pathophysiology
    Brinda Ravikumar
    Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom
    Physiol Rev 90:1383-435. 2010
    ..Finally, we consider the possibility of autophagy upregulation as a therapeutic approach for various conditions...
  98. doi Targeting PI3K signalling in cancer: opportunities, challenges and limitations
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02129, USA
    Nat Rev Cancer 9:550-62. 2009
    ..I focus on the advantages and drawbacks of different treatment strategies for targeting this pathway, the cancers that might respond best to these therapies and the challenges and limitations that confront their clinical development...
  99. ncbi NF-kappaB regulation in the immune system
    Qiutang Li
    The Salk Institute, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Immunol 2:725-34. 2002
    ..We also discuss the role of NF-kappaB proteins as potential therapeutic targets in clinical applications...
  100. pmc Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress
    Shomit Sengupta
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell 40:310-22. 2010
    ..This review focuses on the key components of the mTOR complex 1 pathway and on how various stresses impinge upon them...

Research Grants75

  1. Novel TIRF microscopy analyzing trafficking & signaling at the cell cortex
    Derek Toomre; Fiscal Year: 2009
    ..Consistent with the recovery act's goal, this funding will provide full-time summer employment for 4 undergraduate students and accelerate scientific achievement of the parent DP2 award...
  2. NIH Director's Pioneer Award
    ERICH JARVIS; Fiscal Year: 2009
    ..Repairing the pathway in vocal learners, when damaged, would have profound impact for correcting neurological disorders of speech. ..
  3. Mapping for Specialized Domains for FCeRI Signaling &Internalization
    Bridget S Wilson; Fiscal Year: 2013
    ..Molecular segregation can occur within islands, facilitating signal transduction and at least two pathways of endocytosis...
  4. H1R Signaling and Immune Deviation in EAE
    Cory Teuscher; Fiscal Year: 2013
    ..This domain is associated with signal transduction, but may also be important in protein folding and trafficking, like the intracellular domains of other G-..
  5. Prevention of Acute Lung Injury by IL-6 activated STAT3
    Ana Moran; Fiscal Year: 2010
    ..First, Dr. Tweardy has made significant contributions in Stat3 signal transduction and has ongoing research in this area...
  6. Targeting Galectin-3 with novel drugs for treatment of eczema
    Fu Tong Liu; Fiscal Year: 2010
    ..functions have been demonstrated by using exogenously added galectin-3, which can induce transmembrane signal transduction by crosslinking cell surface glycans...
  7. Regulation of B Cell Function by Membrane-Cytoskeletal Remodeling
    Neetu Gupta; Fiscal Year: 2012
    B cells respond to environmental antigens by assembling signalosomes at the plasma membrane for signal transduction. They migrate throughout the body for surveillance, and interact with T cells and dendritic cells within lymphoid tissue ..
  8. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..activate ion transporters;regulate endocytosis, exocytosis and vesicular trafficking;and are components of signal transduction pathways essential for growth and development...
  9. Patient-Derived Stem Cells for Phosphoproteomic Profiling Neuropsychopathology
    Dieter A Wolf; Fiscal Year: 2011
    ..analysis of hESCs (the 1st such analysis in the field) to identify key (including novel) drugable signal transduction pathways that influence neural differentiation...
  10. Translational Machinery in Stress Signaling and Tumor Suppression
    THOMAS J contact BEGLEY; Fiscal Year: 2010
    ..of cell cycle and apoptotic proteins, as part of the ER stress response, will be ascertained to define signal transduction pathways associated with tumor suppression...
  11. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
    ..work supported by this grant has been to elucidate the potential role that changes in myocardial insulin signal transduction would play in contributing to cardiac dysfunction in obesity and diabetes...
  12. Mitochondrial Dysfunction and Adipose Insulin Resistance
    David A Bernlohr; Fiscal Year: 2013
    ..the antioxidant defense system in adipose cells with mitochondrial function, oxidative phosphorylation, signal transduction and the development of insulin resistance...
  13. Trichothecene Toxicity and the Ribotoxic Stress Response
    James J Pestka; Fiscal Year: 2012
    ..Thus, a critical gap exists in our knowledge of the signal transduction mechanisms by which ribotoxins modulate gene expression and apoptosis...
  14. REGULATION OF GENE EXPRESSION BY DIETARY FAT
    Lisa M Salati; Fiscal Year: 2012
    ..In the course of these studies, we will define intracellular signal transduction pathways by which nutrients and nutritional status can alter the activity or abundance of splicing ..
  15. Monitoring cellular redox signaling and oxidant stress in vivo
    Paul T Schumacker; Fiscal Year: 2010
    Healthy cells use low levels of reactive oxygen species (ROS) as second messengers in signal transduction pathways. High levels of ROS cause oxidative damage to proteins, lipids and DNA...
  16. Enzymatic Regulation of S-Glutathionylation : Role in Apoptosis and Disease
    John J Mieyal; Fiscal Year: 2012
    ..The concepts and pathways of redox signal transduction, which are the focal point of research in the principal investigator's laboratory, were not well known ..
  17. Molecular Regulation of Progesterone Synthesis
    John S Davis; Fiscal Year: 2013
    ..Understanding signaling these cellular processes is vital to understand the integration of signal transduction pathways that control steroidogenesis in endocrine cells...
  18. Sex Steroid Hormone Regulation of Drug Reinforcement
    Diane Lebesgue; Fiscal Year: 2012
    As a student, postdoctoral fellow and instructor, I have studied the molecular biology and signal transduction mechanisms of G protein coupled receptors (GPCRs)...
  19. A novel peroxidase in vascular endothelium and the development of atherosclerosis
    Guangjie Cheng; Fiscal Year: 2012
    ..important roles in physiology, immunology and pathology such as killing of bacteria, modulation of cell signal transduction pathway and tissue damage...
  20. MOLECULAR MECHANISMS OF COMPLEX MIXTURE TOXICITY
    Alvaro Puga; Fiscal Year: 2013
    ..Similarly, sustained exposure to low doses of chromium leads to gradual changes in histone marks and signal transduction pathways that cumulatively affect gene expression and silencing...
  21. Global regulatory interactions in bacterial pathogenesis
    BRIAN AKERLEY; Fiscal Year: 2009
    ..The molecular interactions with the host that necessitate signal transduction by bacteria and the cues they utilize to respond appropriately are not well defined...
  22. Pathogenesis of the Metabolic Syndrome
    W Timothy Garvey; Fiscal Year: 2013
    ..NF-:B), which then phosphorylate insulin receptor substrate (IRS) molecules resulting in impaired insulin signal transduction. However, our preliminary data point to an alternative or complementary pathophysiological process...
  23. Interdisciplinary Research Training in Reproduction for Indian Fellows
    John C Herr; Fiscal Year: 2010
    ..The broad basic themes of faculty research programs include: the molecular analysis of sperm-egg fusion, signal transduction mechanisms between membrane receptors, sperm capacitation and the acrosome reaction, protein transcription, ..
  24. Chronic Stress and Abdominal Pain: Novel Mechanisms
    John W Wiley; Fiscal Year: 2013
    ..Confirmation of the role of specific receptors and signal transduction pathways to the changes observed in CB and TRP pathways will be confirmed using targeted delivery of gene ..
  25. Mechanisms of Endothelin 1-Induced Sickle Cell Pathology
    Alicia Rivera; Fiscal Year: 2011
    ..of cell viability by regulating numerous cellular processes and functions, including metabolism, signal transduction, and transcription...
  26. Biochemistry and Function of a Novel Bacterial Photosensory Two-Component System
    MELISSA MARKS; Fiscal Year: 2010
    ..networks that control physiological and developmental transitions in bacteria largely use two-component signal transduction systems, consisting of histidine protein kinases and their cognate response regulator proteins...
  27. BBP (Bone Morphogenetic Protein Binding Peptide) and Bone Healing
    SAMUEL SCOTT MURRAY; Fiscal Year: 2013
    ..In Specific Aim 2, we will determine the effects of spp24 degradation on TGF-b signal transduction mediated by Smad-dependent pathways, assessed as R-Smad phosphorylation and nuclear translocation...
  28. Novel Reagents and Methods for Rapid and High Throughput Detection of Aflatoxin C
    ALAN AI PING WEI; Fiscal Year: 2013
    ..We propose to develop technologies that can combine molecular recognition with signal transduction, and that are amendable to robust, reproducible automated and high throughput assays...
  29. PTEN TUMOR SUPPRESSOR AND SIGNAL TRANSDUCTION
    RAMON E PARSONS; Fiscal Year: 2012
    ..09/04) Page 4 Form Page 3 ..
  30. 4th ASM Conference on Prokaryotic Cell Biology and Development
    Susan S Golden; Fiscal Year: 2012
    ..and form biofilms by means of sophisticated intercellular communication systems and intracellular signal transduction pathways...
  31. Mitochondrial Dysfunction and Adipose Insulin Resistance
    DAVID BERNLOHR; Fiscal Year: 2009
    ..the antioxidant defense system in adipose cells with mitochondrial function, oxidative phosphorylation, signal transduction and the development of insulin resistance...
  32. Diverse Roles for RIC8 During G Protein Signaling in Fungi
    Katherine A Borkovich; Fiscal Year: 2012
    Heterotrimeric (a??) G proteins are essential components of signal transduction pathways that regulate environmental sensing, growth and development in eukaryotes...
  33. Potential Mechanisms of Glucagon-like peptide-1 in Fatty Liver Disease
    Frank A Anania; Fiscal Year: 2010
    ..binding characteristics, (ii) measurement of cAMP production, and (iii) elucidation of other hepatocyte signal transduction proteins phosphorylated by GLP-1...
  34. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
    ..We use a combination of extensive biochemistry and molecular cell biology to explore the signal transduction mechanisms involved in BAAT1/ATM activation after DNA damage induced by ionizing radiation (IR) and ..
  35. RSK-2 regulates integrin-mediated adhesion and migration
    JOE WILLIAM RAMOS; Fiscal Year: 2013
    ..for ligand (activation) is important in a broad array of cellular functions including adhesion, migration, signal transduction, and the assembly of extracellular matrices...
  36. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    b>Signal transduction from cell-surface members of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR), tumor necrosis factor receptor (TNFR), and immunoglobulin (Ig) superfamilies coordinates the host defense against microbial ..
  37. Lipid Binding Proteins in Obesity and Diabetes Syndromes
    David A Bernlohr; Fiscal Year: 2013
    ..3. Evaluate the interaction of FABPs with LTA4 and LTA4 metabolizing enzymes. 4. Examine the effects of leukotrienes on macrophage and adipocyte signal transduction and cytokine synthesis.
  38. Regulation of Astrocyte TIMP-1 in HIV-Associated Dementia
    JEREL ADAM FIELDS; Fiscal Year: 2011
    ..2 in activated primary human astrocytes and their influence on TIMP-1 transcription and Aim 2 identify signal transduction pathways leading to TIMP-1 down regulation in primary human astrocytes...
  39. BMP signaling in vertebrate development
    Ken W Y Cho; Fiscal Year: 2013
    ..This knowledge has led to the concept of a "core" pathway that mediates BMP signal transduction to control target gene expression...
  40. Transcriptional control of pituitary gonadotropin genes
    Varykina G Thackray; Fiscal Year: 2013
    ..Specific Aim 3 will address mechanisms of insulin signal transduction via FoxO1 in gonadotrope cells and determine if disruption of insulin regulation of FoxO1 impacts fertility ..
  41. Regulation of PTHrP in Squamous Cell Carcinoma by the EGF Receptor
    GWENDOLEN LORCH; Fiscal Year: 2010
    ..goal is to investigate epidermal growth factor receptor (EGFR) kinase signaling that leads to perturbed signal transduction and increased parathyroid hormone-related protein (PTHrP) expression and humoral hypercalcemia of ..
  42. Mechanisms of TGFB Signal Transduction
    Akiko Hata; Fiscal Year: 2013
    ..Germline mutations of the type II BMP receptor (BMPRII) gene are associated with IPAH. By studying a protein called FHL2 that interacts with BMPRII and regulates BMPRII function, this application will investigate the etiology of IPAH. ..
  43. KCNQ Channels and Vasoconstrictor Signal Transduction
    Kenneth L Byron; Fiscal Year: 2013
    ..Although KCNQ channels had not previously been considered to play a role in vasoconstrictor signal transduction, we have recently shown that suggest that regulation of arterial myocyte excitability by physiological ..
  44. Genetic Study of PP-Fold Polypeptide-Receptor Axis on Metabolic Syndrome Risk
    PEI AN SHIH; Fiscal Year: 2013
    ..obesity and MetS risk after atypical antipsychotic (ATAP) treatment, and assess ATAP effects on PYY pathway signal transduction in vitro...
  45. The PKCepsilon-regulated oncogenic and tumor suppressor roles of ATF2 in melanoma
    ERIC KIRK LAU; Fiscal Year: 2013
    ..expedite the further development of my scientific and technical expertise, and my transition into a successful, independent research faculty in transcriptional control, protein signal transduction, melanoma and cancer.
  46. Lifespan Extension Despite Greatly Elevated Insulin and Body Fat
    David E Harrison; Fiscal Year: 2013
    ..b>Signal transduction, fuel utilization, and adipose tissue markers that differ between DR-OB and DR +/? will identify candidate ..
  47. Redox regulation of phagocyte NOX2 in inflammation and aging
    Robert A Clark; Fiscal Year: 2013
    ..Three specific aims will guide the work. Aim 1 is to dissect the proximal elements of this signal transduction pathway as a means of defining the early targets of H2O2, focusing on the H2O2-activated Ca2+ channels ..
  48. Cellular and Molecular Regulation of Thrombopoiesis
    Ramesh A Shivdasani; Fiscal Year: 2012
    ..to visualize platelet release in living Myh9-null mice, and biochemical and functional analysis of signal transduction in cultured primary mouse MKs to evaluate the role of Sdf-1...
  49. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2012
    ..models of STZ-induced uDM that enable us to identify the specific brain areas and neuronal subsets in which signal transduction via the IRS-PI3K-PKB pathway regulates food intake and glucose metabolism...
  50. Mechanistic Characterization and Genetic Analysis of Systemic Iron Homeostasis
    Xin Du; Fiscal Year: 2011
    ..the cytoplasmic domain of TMPRSS6 is able to autonomously drive the suppressive signal transduction. In addition, we investigated the transcription profiles in HepG2 cells (a liver carcinoma cell line) with ..
  51. Regulation of IFN-beta induction by P2X7 purinergic receptor signaling
    JUDITH ANNE SMITH; Fiscal Year: 2011
    ..to determine whether P2X7 enhancement is LPS specific. P2X7 ligation is known to initiate multiple signal transduction pathways: the contribution of calcium and MAP-kinase signaling pathways to the effect of BzATP on IFN- [..
  52. Modulation of Natriuretic Peptides via Caveolin in Hypertrophy and Heart Failure.
    David M Roth; Fiscal Year: 2013
    ..signaling involved in cardiac hypertrophy is complex and involves a number of cell surface receptors, signal transduction pathways and nuclear factors...
  53. ANGIOTENSIN II SIGNAL TRANSDUCTION
    Bradford C Berk; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: The healing of tissues after surgery or trauma is critical for long-term survival. The proposed work will study novel mechanisms by which blood vessels grow in response to tissue injury. ..
  54. Defining the molecular determinants of the threshold for autoimmune arthritis
    Lih Yun Hsu; Fiscal Year: 2013
    ..in laboratory based research focused on the mechanisms of autoimmune diseases caused by dysregulated signal transduction in immune cells...
  55. Lipid Binding Proteins in Obesity and Diabetes Syndromes
    David A Bernlohr; Fiscal Year: 2011
    ..3. Assess the role of fatty acid binding proteins in leukotriene biosynthesis. 4. Examine the effect of leukotrienes on adipocyte and macrophage signal transduction and metabolism.
  56. Regulation of Human Papillomavirus Replication via Cell Signaling Pathways
    ANASTACIA GRIEGO; Fiscal Year: 2013
    ..We posit that HPV-mediated gene expression results in increased EGFR signal transduction leading to enhanced viral transcription through modulation of cell survival and proliferation signals...
  57. Developing a murine model for arsenic-induced skin neoplasm
    Mohammad Athar; Fiscal Year: 2010
    ..The Shh signaling pathway is one of the most fundamental signal transduction pathways during embryonic development...
  58. CONTROL OF EUCARYOTIC FUNCTION BY METHYLATION
    Steven G Clarke; Fiscal Year: 2013
    ..We are especially interested in methyltransferases that are involved in signal transduction and metabolic regulatory pathways where the presence or absence of the methyl group can modulate the ..
  59. Signal Transduction Mechanism of Osteoclast Differentiation
    Nandini Ghosh-Choudhury; Fiscal Year: 2013
    ..Our results will demonstrate how BMP-2 can orchestrate a complex transcriptional network in osteoblasts to tightly regulate osteoclast activation. ..
  60. PLD2, as a GEF or as a Lipase, is Central to Leukocyte Chemotaxis
    JULIAN G CAMBRONERO; Fiscal Year: 2013
    ..We will also ascertain the PLD regulatory mechanisms of signal transduction that operate in vivo...
  61. High-affinity RNA targets of Survival Motor Neuron Protein
    Ravindra N Singh; Fiscal Year: 2013
    ..of small-nuclear ribonucleoproteins (snRNPs), transcription, pre-mRNA splicing, macromolecular trafficking, signal transduction and stress granule formation...
  62. MIF AND THE HOST RESPONSE TO INFECTION
    RICHARD J BUCALA; Fiscal Year: 2013
    ..to require a complex of two transmembrane proteins: one mediating MIF-binding (CD74), and one initiating signal transduction (CD44)...
  63. BRAINSTEM MATURATION IN THE SUDDEN INFANT DEATH SYNDROME
    HANNAH CHASE KINNEY; Fiscal Year: 2013
    ..because they are directly relevant to 5-HT neurotransmission: 1) 14-3-3 proteins which are involved in signal transduction, including in regulation of TPH2;and 2) certain synaptic proteins, including 3-synuclein, actin, and ..
  64. Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea
    Sharona E Gordon; Fiscal Year: 2013
    ....
  65. NAD Metabolism and Signaling
    Frances E Lund; Fiscal Year: 2011
    ..It was largely believed that NAD and its related metabolites were too abundant to function in a signal transduction capacity and that they were therefore unlikely to be involved in regulating cellular functions...
  66. ADIPOCYTE PROTEIN SECRETION AND INSULIN ACTION
    Harvey Lodish; Fiscal Year: 2007
    ..The PI will examine the involvement of signal transduction systems in regulating ARCP30 and GLUT4 vesicular traffic, in particular those utilized by insulin and ..
  67. Signal transduction in TRPM5-expressing olfactory sensory neurons
    Diego Restrepo; Fiscal Year: 2010
    ..In recent work in the Restrepo laboratory we show that signal transduction for pheromones and other biologically relevant odors in the MOE involves the transient receptor potential ..
  68. Global Regulation of Gene expression in Streptococcus pneumoniae
    Bernard Weisblum; Fiscal Year: 2010
    ..Mortality and morbidity due to S. pneumoniae is seen primarily in the very young and elderly. Signal transduction plays a major role in sensing the environment of S. pneumoniae and in its decision to become pathogenic...
  69. EFFECTS OF ETHANOL ON PHOSPHOLIPASE D MEDIATED SIGNALING
    Joel Horwitz; Fiscal Year: 2003
    Chronic ethanol consumption has profound effects on signal transduction. Our long-term objectives are to understand the effects of chronic ethanol exposure on signal transduction in neuronal systems in order to elucidate the mechanisms ..
  70. Acute Nutritional Deprivation: Diaphragm Influences
    Michael Lewis; Fiscal Year: 2007
    ..Hypothesis 1: Down-regulation of the PI3K/Akt/mTOR signal transduction pathway is an important determinant of disordered synthesis of muscle proteins and atrophy with ND...
  71. REGULATION OF GRANULOCYTE AND MACROPHAGE PRODUCTION
    E Stanley; Fiscal Year: 2001
    ..The specific aims are: 1. To identify novel components of CSF-1 signal transduction pathways. 2. To elucidate the functions of components of CSF-1 signal transduction pathways. 3...
  72. Naturally Occurring Agent for Alcohol Liver Diseases
    YUE WEI LEE; Fiscal Year: 2003
    ..liver diseases, it is essential to understand, at the molecular level, potential alterations in cellular signal transduction pathways that adversely affect the hepatocyte proliferative response, as well as those survival mechanisms ..
  73. ADP RIBOSYLATION OF A POTENT INDUCER OF PROLIFERATION
    Mark Francis; Fiscal Year: 2002
    ..Adapted from Investigator's abstract): The broad goal of the proposed study is to improve understanding of signal transduction pathways involved in B cell activation...
  74. TNF ALPHA REG OF THE GROWTH HORMONE/IGF-1 AXIS WITH AGE
    William Sonntag; Fiscal Year: 2000
    ..Adapted from the Applicant's Abstract): A number of studies clearly suggest that a general decline in signal transduction and, specifically, a decline in growth hormone signal transduction, are critical aspects of biological ..
  75. Ras and Chemokine Stimulated Neutrophil Polarization
    Cindy Knall; Fiscal Year: 2004
    ..Research is beginning to investigate the specific signal transduction pathways activated by these chemokines to regulate neutrophil functions...