map kinase signaling system

Summary

Summary: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.

Top Publications

  1. ncbi Mammalian MAP kinase signalling cascades
    L Chang
    Department of Pharmacology, University of California San Diego, La Jolla 92093-0636, USA
    Nature 410:37-40. 2001
  2. ncbi Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation
    J M Kyriakis
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
    Physiol Rev 81:807-69. 2001
  3. ncbi Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions
    G Pearson
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Endocr Rev 22:153-83. 2001
  4. ncbi MAP kinase signalling cascade in Arabidopsis innate immunity
    Tsuneaki Asai
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 415:977-83. 2002
  5. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
  6. ncbi Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
    P J Roberts
    Division of Pharmacotherapy and Experimental Therapeutics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Oncogene 26:3291-310. 2007
  7. ncbi Signal integration by JNK and p38 MAPK pathways in cancer development
    Erwin F Wagner
    Centro Nacional de Investigaciones Oncologicas, C Melchor Fernandez Almagro 3, Madrid 28029, Spain
    Nat Rev Cancer 9:537-49. 2009
  8. ncbi Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases
    Gary L Johnson
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Science 298:1911-2. 2002
  9. pmc COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
    Cory M Johannessen
    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 468:968-72. 2010
  10. ncbi Signal transduction by the JNK group of MAP kinases
    R J Davis
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605, USA
    Cell 103:239-52. 2000

Research Grants

  1. MECHANISMS OF HEMORRHAGE AND EDEMA IN TPA STROKE THERAPY
    ENG LO; Fiscal Year: 2006
  2. STRETCH-INDUCED CYCLOOXYGENASE-2 IN UROTHELIAL CELLs
    Stephen Nakada; Fiscal Year: 2005
  3. Signaling Pathways in Pathogenesis of Renal Fibrosis
    JOSEPH GRANDE; Fiscal Year: 2004
  4. Signaling Mechanisms of TCDD-induced AHR Activation
    Ying Xia; Fiscal Year: 2007
  5. NLR signaling in colitis and colorectal tumorigenesis
    Thirumala Devi Kanneganti; Fiscal Year: 2013
  6. Interactions and Dual Phosphorylation in MAP Kinase Cascades
    Elizabeth J Goldsmith; Fiscal Year: 2010
  7. Muller glia and neuronal regeneration in the retina
    Andy Fischer; Fiscal Year: 2009
  8. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
  9. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
  10. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006

Detail Information

Publications293 found, 100 shown here

  1. ncbi Mammalian MAP kinase signalling cascades
    L Chang
    Department of Pharmacology, University of California San Diego, La Jolla 92093-0636, USA
    Nature 410:37-40. 2001
    ....
  2. ncbi Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation
    J M Kyriakis
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
    Physiol Rev 81:807-69. 2001
    ..The nuclear factor-kappa B pathway, a second stress signaling paradigm, has been the subject of several excellent recent reviews (258, 260)...
  3. ncbi Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions
    G Pearson
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Endocr Rev 22:153-83. 2001
    ..This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2...
  4. ncbi MAP kinase signalling cascade in Arabidopsis innate immunity
    Tsuneaki Asai
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 415:977-83. 2002
    ..Activation of this MAPK cascade confers resistance to both bacterial and fungal pathogens, suggesting that signalling events initiated by diverse pathogens converge into a conserved MAPK cascade...
  5. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
    ..As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma...
  6. ncbi Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
    P J Roberts
    Division of Pharmacotherapy and Experimental Therapeutics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Oncogene 26:3291-310. 2007
    ..In this review, we summarize the current status of the different approaches and targets that are under evaluation and development for the therapeutic intervention of this key signaling pathway in human disease...
  7. ncbi Signal integration by JNK and p38 MAPK pathways in cancer development
    Erwin F Wagner
    Centro Nacional de Investigaciones Oncologicas, C Melchor Fernandez Almagro 3, Madrid 28029, Spain
    Nat Rev Cancer 9:537-49. 2009
    ..In this Review we highlight the recent progress made in defining the functions of the JNK and p38 MAPK pathways in different cancers...
  8. ncbi Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases
    Gary L Johnson
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Science 298:1911-2. 2002
    ..The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity...
  9. pmc COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
    Cory M Johannessen
    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 468:968-72. 2010
    ....
  10. ncbi Signal transduction by the JNK group of MAP kinases
    R J Davis
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605, USA
    Cell 103:239-52. 2000
  11. pmc Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
    Arkaitz Carracedo
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:3065-74. 2008
    ....
  12. pmc Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance
    James A McCubrey
    Department of Microbiology and Immunology, Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Biochim Biophys Acta 1773:1263-84. 2007
    ....
  13. ncbi MAP kinase signalling pathways in cancer
    A S Dhillon
    The Beatson Institute for Cancer Research, Bearsden, Glasgow, UK
    Oncogene 26:3279-90. 2007
    ..The balance and integration between these signals may widely vary in different tumours, but are important for the outcome and the sensitivity to drug therapy...
  14. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
    ..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...
  15. pmc Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers
    Jeffrey A Engelman
    Nat Med 14:1351-6. 2008
    ..These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers...
  16. pmc RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
    Poulikos I Poulikakos
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 464:427-30. 2010
    ..In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS...
  17. ncbi Hyperactive Ras in developmental disorders and cancer
    Suzanne Schubbert
    Department of Pediatrics, University of California, 513 Parnassus Avenue, Room HSE 302, San Francisco, California 94143, USA
    Nat Rev Cancer 7:295-308. 2007
    ..Here we will discuss the implications of germline mutations in the Ras-Raf-MEK-ERK pathway for understanding normal developmental processes and cancer pathogenesis...
  18. ncbi Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival
    Melissa R Junttila
    Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland
    FASEB J 22:954-65. 2008
    ..In addition, we will discuss the potential functional relevance of negative regulation of ERK pathway activity, for physiological and pathological conditions (e.g., cellular transformation)...
  19. ncbi MAPK signal pathways in the regulation of cell proliferation in mammalian cells
    Wei Zhang
    The Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, China
    Cell Res 12:9-18. 2002
    ..The above effects are fulfilled by regulation of cell cycle engine and other cell proliferation related proteins. In this paper we discussed their functions and cooperation with other signal pathways in regulation of cell proliferation...
  20. ncbi Pathological roles of MAPK signaling pathways in human diseases
    Eun Kyung Kim
    School of Life Sciences and Biotechnology, Korea University, Seoul 136 701, South Korea
    Biochim Biophys Acta 1802:396-405. 2010
    ..In this review, we summarize recent findings on the roles of MAPK signaling pathways in human disorders, focusing on cancer and neurodegenerative diseases including AD, PD, and ALS...
  21. ncbi Mitogen-activated protein kinase signaling in plants
    Maria Cristina Suarez Rodriguez
    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    Annu Rev Plant Biol 61:621-49. 2010
    ..Future work needs to focus on identifying substrates of MAPKs, and on understanding how specificity is achieved among MAPK signaling pathways...
  22. ncbi Differential regulation and properties of MAPKs
    M Raman
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
    Oncogene 26:3100-12. 2007
    ..Here, we describe some of the properties of the three major MAPK pathways and discuss how these properties govern pathway regulation and activity...
  23. ncbi Mitogen-activated protein kinases in apoptosis regulation
    Teiji Wada
    IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohr gasse3 5, Vienna A 1030, Austria
    Oncogene 23:2838-49. 2004
    ..In this review, we discuss MAPKs in apoptosis regulation with attention to mouse genetic models and critically point out the multiple roles of MAPKs...
  24. ncbi The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition
    S Meloche
    Departments of Pharmacology and Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec, Canada
    Oncogene 26:3227-39. 2007
    ..In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells. We also highlight the findings obtained from gene disruption studies...
  25. ncbi Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms
    A Bonni
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Science 286:1358-62. 1999
    ....
  26. ncbi FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment
    Tilo Kunath
    Centre Development in Stem Cell Biology, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
    Development 134:2895-902. 2007
    ....
  27. pmc Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model
    Carolyn Waugh Kinkade
    Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 118:3051-64. 2008
    ..We therefore propose that combination therapy targeting AKT/mTOR and ERK MAPK signaling pathways may be an effective treatment for patients with advanced prostate cancer, in particular those with hormone-refractory disease...
  28. ncbi Activation and signaling of the p38 MAP kinase pathway
    Tyler Zarubin
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Res 15:11-8. 2005
    ..Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38...
  29. ncbi Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases
    D M Owens
    Cancer Research UK Stress Response Laboratory, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK
    Oncogene 26:3203-13. 2007
    ....
  30. pmc Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale
    Beth A Rose
    Departments of Anesthesiology, Physiology, and Medicine, David Geffen School of Medicine, Molecular Biology, Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA
    Physiol Rev 90:1507-46. 2010
    ....
  31. ncbi FAK integrates growth-factor and integrin signals to promote cell migration
    D J Sieg
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nat Cell Biol 2:249-56. 2000
    ..Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways...
  32. ncbi AP-1 as a regulator of cell life and death
    Eitan Shaulian
    Department of Experimental Medicine and Cancer Research, School of Medicine, The Hebrew University, Jerusalem, 91120, Israel
    Nat Cell Biol 4:E131-6. 2002
    ..Mostly, c-Jun is a positive regulator of cell proliferation, whereas JunB has the converse effect. The intricate relationships between the different Jun proteins, their activities and the mechanisms that mediate them will be discussed...
  33. ncbi The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions
    Yonat Keshet
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Methods Mol Biol 661:3-38. 2010
    ..Mis-regulation of the MAPKs signals usually leads to diseases such as cancer and diabetes; therefore, studying the mechanisms of specificity-determination may lead to better understanding of these signaling-related diseases...
  34. ncbi The role of signaling pathways in the development and treatment of hepatocellular carcinoma
    S Whittaker
    Dana Farber Cancer Institute, Boston, MA, USA
    Oncogene 29:4989-5005. 2010
    ..In addition, we also review the latest preclinical and clinical data on the rationally designed targeted agents that are now being directed against these pathways, with early evidence of success...
  35. pmc A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila
    E Shlevkov
    Centro de Biologia Molecular, Consejo Superior de Investigaciones Cientificas UAM, Madrid, Spain
    Cell Death Differ 19:451-60. 2012
    ..Thus, our results indicate that stress-induced apoptosis in Drosophila is dependant on an amplification loop mediated by dp53 and JNK. Furthermore, they also demonstrate a mechanism of mutual activation of proapoptotic genes...
  36. pmc Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo
    Jennifer Nichols
    Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
    Development 136:3215-22. 2009
    ..We propose that ES cells are not a tissue culture creation, but are essentially identical to pre-implantation epiblast cells...
  37. pmc MAP kinase and pain
    Ru Rong Ji
    Pain Research Center, Department of Anesthesiology, Brigham and Women s Hospital and Harvard Medical School, 75 Francis Street, MRB 604, Boston, MA 02115, USA
    Brain Res Rev 60:135-48. 2009
    ..Although it is well documented that MAPK pathways can increase pain sensitivity via peripheral mechanisms, this review will focus on central mechanisms of MAPKs, especially ERK...
  38. ncbi p38 MAP-kinases pathway regulation, function and role in human diseases
    Ana Cuenda
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochim Biophys Acta 1773:1358-75. 2007
    ..Here we focus on these emergent roles of p38MAPKs and their implication in different pathologies...
  39. ncbi Comparative genomics of MAP kinase and calcium-calcineurin signalling components in plant and human pathogenic fungi
    Nicolas Rispail
    Departamento de Genetica, Universidad de Cordoba, Cordoba, Spain
    Fungal Genet Biol 46:287-98. 2009
    ..cerevisiae signalling proteins, most likely reflect functional diversification or adaptation as filamentous fungi have evolved to occupy distinct ecological niches...
  40. ncbi Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate
    Silvia D M Santos
    European Molecular Biology Laboratory EMBL, Cell Biology and Biophysics, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nat Cell Biol 9:324-30. 2007
    ..These results show that growth factor context determines the topology of the MAPK signalling network and that the resulting dynamics govern cell fate...
  41. ncbi The JNK signal transduction pathway
    Claire R Weston
    Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Curr Opin Cell Biol 19:142-9. 2007
    ..Roles of novel molecules that participate in the JNK pathway have been defined and new insight into the role of JNK in survival signaling, cell death, cancer and diabetes has been achieved...
  42. ncbi Reactive oxygen species-induced activation of the MAP kinase signaling pathways
    James A McCubrey
    Department of Microbiology and Immunology, and the Leo W Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Antioxid Redox Signal 8:1775-89. 2006
    ..The purpose of this review is to provide the reader with an overall understanding and appreciation of oxidative stress-induced MAPK signaling...
  43. ncbi Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions
    Hector Peinado
    Instituto de Investigaciones Biomédicas Alberto Sols CSIC UAM and Departamento de Bioquímica UAM, Arturo Duperier 4, 28029 Madrid, Spain
    J Biol Chem 278:21113-23. 2003
    ..These data support that MAPK and phosphatidylinositol 3-kinase signaling pathways are implicated in TGFbeta1-mediated induction of Snail promoter, probably through Ras activation and its downstream effectors...
  44. pmc Dual control of nuclear EIN3 by bifurcate MAPK cascades in C2H4 signalling
    Sang Dong Yoo
    Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 451:789-95. 2008
    ..The results suggest a new paradigm for linking intertwined MAPK cascades to control quantitative responses and specificity in signalling networks...
  45. ncbi TAK1 is a ubiquitin-dependent kinase of MKK and IKK
    C Wang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 412:346-51. 2001
    ..We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK...
  46. pmc Stomatal development and patterning are regulated by environmentally responsive mitogen-activated protein kinases in Arabidopsis
    Huachun Wang
    Division of Biological Sciences, University of Missouri, Columbia, Missouri 65211, USA
    Plant Cell 19:63-73. 2007
    ....
  47. pmc Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health
    William H Chappell
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, USA
    Oncotarget 2:135-64. 2011
    ..Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging...
  48. ncbi MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits
    Bozena Kaminska
    Department of Cell Biology, Laboratory of Transcription Regulation, Nencki Institute of Experimental Biology, 3 Pasteur Str, 02 093 Warsaw, Poland
    Biochim Biophys Acta 1754:253-62. 2005
    ..Moreover, many of these drugs are small molecules that can be administered orally, and initial results of clinical trials have shown clinical benefits in patients with chronic inflammatory disease...
  49. pmc Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae
    Raymond E Chen
    Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3202, USA
    Biochim Biophys Acta 1773:1311-40. 2007
    ....
  50. ncbi MEKK1 is required for MPK4 activation and regulates tissue-specific and temperature-dependent cell death in Arabidopsis
    Kazuya Ichimura
    Sainsbury Laboratory, John Innes Centre, Colney Lane, Norwich NR4 7UH, United Kingdom
    J Biol Chem 281:36969-76. 2006
    ....
  51. ncbi A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity
    Dennis H Kim
    Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
    Science 297:623-6. 2002
    ..These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species...
  52. pmc The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response
    Hideki Inoue
    Department of Molecular Biology, Graduate School of Science, Institute for Advanced Research, Nagoya University, Chikusa ku, Nagoya 464 8602, Japan
    Genes Dev 19:2278-83. 2005
    ..These results delineate the C. elegans p38 MAPK signaling pathway leading to the nucleus that responds to oxidative stress...
  53. pmc Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
    Gideon Bollag
    Plexxikon Inc, 91 Bolivar Drive, Berkeley, California 94710, USA
    Nature 467:596-9. 2010
    ..These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity...
  54. ncbi The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory
    J D Sweatt
    Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030 3498, USA
    J Neurochem 76:1-10. 2001
    ..Finally, I will speculate on what the critical downstream effectors of the erks are in neurons, and how they might provide a readout of the integrated signal...
  55. pmc Rewired ERK-JNK signaling pathways in melanoma
    Pablo Lopez-Bergami
    Signal Transduction Program, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cancer Cell 11:447-60. 2007
    ..Our data reveal that, in human melanoma, the rewired ERK signaling pathway upregulates JNK and activates the c-Jun oncogene and its downstream targets, including RACK1 and cyclin D1...
  56. pmc Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades
    Nick I Markevich
    Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, USA
    J Cell Biol 164:353-9. 2004
    ..Hence, bistability induced by multisite covalent modification may be a widespread mechanism of the control of protein activity...
  57. ncbi Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression
    Klaus P Hoeflich
    Department of Cancer Signaling and Translational Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Cancer Res 69:3042-51. 2009
    ..Taken together, these studies increase our understanding of the molecular determinants for antitumor efficacy resulting from RAF pathway inhibition and have implications for therapeutic intervention in the clinic...
  58. pmc A systems-level analysis of perfect adaptation in yeast osmoregulation
    Dale Muzzey
    Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 138:160-71. 2009
    ..We conclude that the system contains only one effective integrating mechanism, which requires Hog1 kinase activity and regulates glycerol synthesis but not leakage...
  59. pmc Scaffold number in yeast signaling system sets tradeoff between system output and dynamic range
    Ty M Thomson
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 108:20265-70. 2011
    ..Additional analysis and experiment suggest that scaffold abundance sets a tradeoff between maximum system output and system dynamic range, a prediction supported by recent experiments...
  60. ncbi Tumour cell survival signalling by the ERK1/2 pathway
    K Balmanno
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK
    Cell Death Differ 16:368-77. 2009
    ....
  61. ncbi Serine phosphorylation of STATs
    T Decker
    Vienna Biocenter, Institute of Microbiology and Genetics, Dr Bohr Gasse 9, A 1030 Vienna, Austria
    Oncogene 19:2628-37. 2000
    ..The biochemical and biological consequences of STAT serine phosphorylation are discussed. Oncogene (2000)...
  62. pmc S6K1(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5'-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway
    Mario Pende
    Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland
    Mol Cell Biol 24:3112-24. 2004
    ..These data reveal a redundancy between the S6K and the MAPK pathways in mediating early S6 phosphorylation in response to mitogens...
  63. pmc Tunable signal processing in synthetic MAP kinase cascades
    Ellen C O'Shaughnessy
    Howard Hughes Medical Institute, Department of Biomedical Engineering, Center for Advanced Biotechnology, Boston University, MA 02215, USA
    Cell 144:119-31. 2011
    ..This work demonstrates that tunable signal processing is inherent to minimal MAPK modules and elucidates principles for rational design of synthetic signaling systems...
  64. ncbi CD40-modulated dual-specificity phosphatases MAPK phosphatase (MKP)-1 and MKP-3 reciprocally regulate Leishmania major infection
    Neetu Srivastava
    National Centre for Cell Science, Ganeshkhind, Pune 411007, India
    J Immunol 186:5863-72. 2011
    ..The findings reveal a novel parasite-devised immune evasion strategy and an effective target to redirect CD40-regulated immune responses...
  65. ncbi Translational control by MAPK signaling in long-term synaptic plasticity and memory
    Raymond J Kelleher
    Howard Hughes Medical Institute, The Picower Center for Learning and Memory, RIKEN MIT Neuroscience Research Center, Center for Cancer Research, Departments of Biology and Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA
    Cell 116:467-79. 2004
    ..These results suggest a crucial role for translational control by MAPK signaling in long-lasting forms of synaptic plasticity and memory...
  66. ncbi Specific bacterial suppressors of MAMP signaling upstream of MAPKKK in Arabidopsis innate immunity
    Ping He
    Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
    Cell 125:563-75. 2006
    ..Deletions of avrPto and avrPtoB from pathogenic P. syringae reduce its virulence. The studies reveal a fundamental role of MAMP signaling in nonhost immunity, and a novel action of type III effectors from pathogenic bacteria...
  67. ncbi Dynamic control of yeast MAP kinase network by induced association and dissociation between the Ste50 scaffold and the Opy2 membrane anchor
    Katsuyoshi Yamamoto
    Division of Molecular Cell Signaling, Institute of Medical Sciences, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Mol Cell 40:87-98. 2010
    ..Thus, dynamic regulation of Ste50-Opy2 interaction fine-tunes the MAPK signaling network...
  68. pmc Input-output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data
    William W Chen
    Department of Systems Biology, Center for Cell Decision Processes, Harvard Medical School, Boston, MA 02115, USA
    Mol Syst Biol 5:239. 2009
    ..Thus, key system-wide features of ErbB signaling arise from nonlinear interaction among signaling elements, the properties of which appear quite different in context and in isolation...
  69. pmc ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1)
    Audrey Carriere
    Department of Pathology, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
    J Biol Chem 286:567-77. 2011
    ..Our data provide a novel regulatory mechanism by which mitogenic and oncogenic activation of the Ras/MAPK pathway promotes mTOR signaling...
  70. ncbi Anchorage-dependent ERK signaling--mechanisms and consequences
    Alan K Howe
    University of North Carolina, Chapel Hill, School of Medicine, Department of Pharmacology, Campus Box 7365, Chapel Hill, North Carolina 27599 3765, USA
    Curr Opin Genet Dev 12:30-5. 2002
    ..Recent work has demonstrated that cell adhesion can regulate ERK signaling at several checkpoints and has begun to define the mechanism and consequences associated with anchorage-dependent effects on the ERK cascade...
  71. pmc Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling
    Zain Paroo
    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Cell 139:112-22. 2009
    ..Taken together, these studies indicate that the MAPK/Erk pathway regulates the miRNA machinery and suggest a general principle, wherein signaling systems target the miRNA pathway to achieve biological responses...
  72. pmc Integration of a phosphatase cascade with the mitogen-activated protein kinase pathway provides for a novel signal processing function
    Virendra K Chaudhri
    Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India
    J Biol Chem 285:1296-310. 2010
    ..Thus, we identify an added dimension to signal processing wherein the output response to an external stimulus is additionally filtered through indicators that define the phenotypic status of the cell...
  73. ncbi Redox control of cell fate by MAP kinase: physiological roles of ASK1-MAP kinase pathway in stress signaling
    Atsushi Matsuzawa
    Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113 0033, Japan
    Biochim Biophys Acta 1780:1325-36. 2008
    ..In this review, we focus on redox control of cell function by MAP kinase signaling, and provide the advanced mechanism of redox-regulated ASK1 activation and physiological roles of the ASK1-MAP kinase pathway in stress signaling...
  74. ncbi Tumor necrosis factor signaling
    H Wajant
    Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring, Germany
    Cell Death Differ 10:45-65. 2003
    ..In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed...
  75. ncbi Reciprocal CD40 signals through p38MAPK and ERK-1/2 induce counteracting immune responses
    Ram Kumar Mathur
    National Centre for Cell Science, Ganeshkhind, Pune 411007, India
    Nat Med 10:540-4. 2004
    ..These data uncover a new immune evasion strategy, whereby Leishmania differentially modulates CD40-engaged, reciprocally functioning signaling modules, and provide a new conceptual framework for immune homeostasis...
  76. ncbi Diphenyl difluoroketone: a curcumin derivative with potent in vivo anticancer activity
    Dharmalingam Subramaniam
    Section of Digestive Diseases and Nutrition, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126, USA
    Cancer Res 68:1962-9. 2008
    ..Taken together, these data suggest that the novel curcumin-related compound EF24 is a potent antitumor agent that induces caspase-mediated apoptosis during mitosis and has significant therapeutic potential for gastrointestinal cancers...
  77. pmc Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway
    Mohammad Atefi
    Department of Medicine, Division of Hematology Oncology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 6:e28973. 2011
    ..Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway...
  78. ncbi MAP kinase pathways
    Maosong Qi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    J Cell Sci 118:3569-72. 2005
  79. ncbi Protein phosphatases and the regulation of mitogen-activated protein kinase signalling
    S M Keyse
    Molecular Pharmacology Unit, Imperial Cancer Research Fund, Biomedical Research Centre, Level 5, Ninewells Hospital, Dundee, DD1 9SY, UK
    Curr Opin Cell Biol 12:186-92. 2000
    ....
  80. pmc Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway
    Tatsushi Igaki
    Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    EMBO J 21:3009-18. 2002
    ..We also show genetically that Eiger is a physiological ligand for the Drosophila JNK pathway. Our findings demonstrate that Eiger can initiate cell death through an IAP-sensitive cell death pathway via JNK signaling...
  81. pmc Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells
    Neeraj K Saxena
    Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Cancer Res 67:2497-507. 2007
    ..Our findings have potential clinical implications for hepatocellular carcinoma progression in obese patients...
  82. ncbi Spatial and temporal patterns of ERK signaling during mouse embryogenesis
    Laura Beth Corson
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    Development 130:4527-37. 2003
    ..These studies identify key domains of sustained ERK signaling in the intact mouse embryo, give significant insight into the regulation of this signaling in vivo and pinpoint regions where downstream target genes can be sought...
  83. ncbi Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction
    David Teis
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Dev Cell 3:803-14. 2002
    ..Reduction of MP1 or p14 protein levels by siRNAi results in defective signal transduction. Therefore, our results suggest that the endosomal localization of the p14/MP1-MAPK scaffold complex is crucial for signal transduction...
  84. ncbi Ras signalling on the endoplasmic reticulum and the Golgi
    Vi K Chiu
    Department of Medicine, Cell Biology and Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Nat Cell Biol 4:343-50. 2002
    ..Thus, Ras signalling is not limited to the PM, but also proceeds on the endomembrane...
  85. ncbi p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment
    Simona Saccani
    Institute for Research in Biomedicine, Via Vela 6, CH 6501, Bellinzona, Switzerland
    Nat Immunol 3:69-75. 2002
    ..These results show that p38 plays an additional role in the induction of the inflammatory and immune response: the regulation of NF-kappa B recruitment to selected chromatin targets...
  86. pmc Mechanism of p38 MAP kinase activation in vivo
    Deborah Brancho
    Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Genes Dev 17:1969-78. 2003
    ..These data indicate that p38 MAPK is regulated by the coordinated and selective actions of three different protein kinases in response to cytokines and exposure to environmental stress...
  87. ncbi Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells
    Tomoko Hayashida
    Department of Pediatrics, The Feinberg School of Medicine, Northwestern University, W 140, Pediatrics, 303 E Chicago Ave, Ward 12 112, Chicago, Illinois 60611 3008, USA
    FASEB J 17:1576-8. 2003
    ..These results indicate that ERK-dependent R-Smad linker region phosphorylation enhances collagen I synthesis and imply positive cross talk between the ERK and Smad pathways in human mesangial cells...
  88. ncbi Targeting the RAF-MEK-ERK pathway in cancer therapy
    Clara Montagut
    Medical Oncology Department and Cancer Research Program, Hospital del Mar IMIM, Passeig Maritim 25 29, 08003 Barcelona, Spain
    Cancer Lett 283:125-34. 2009
    ....
  89. ncbi The ups and downs of MEK kinase interactions
    C Hagemann
    Department of Cell Physiology and Pharmacology, University of Leicester, Medical Sciences Building, University Road, LE1 9HN, Leicester, UK
    Cell Signal 13:863-75. 2001
    ..This review summarises our current knowledge concerning the regulation and function of MEKK family members, with particular emphasis on those factors capable of directly interacting with distinct MEKK isoforms...
  90. pmc Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload
    Hongliang Li
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
    Proc Natl Acad Sci U S A 107:13818-23. 2010
    ..These studies indicate that Rgs5 protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure...
  91. ncbi MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol
    Aaron M Domina
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA
    Oncogene 23:5301-15. 2004
    ....
  92. ncbi Post-transcriptional regulation of gene expression by mitogen-activated protein kinase p38
    Andrew R Clark
    Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
    FEBS Lett 546:37-44. 2003
    ..This review describes recent progress and remaining puzzles in the field of post-transcriptional regulation by p38...
  93. ncbi CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway
    S Ma
    Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
    Oncogene 27:1749-58. 2008
    ..Targeting of this specific survival signaling pathway in CD133+ HCC CSCs may provide a novel therapeutic model for the disease...
  94. ncbi Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors
    Arati Sharma
    Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Cancer Res 65:2412-21. 2005
    ..Thus, these studies identify the mechanistic underpinnings by which mutant (V599E)B-RAF promotes melanoma development and show the effectiveness of targeting this protein to inhibit melanoma tumor growth...
  95. pmc Participation of the p38 pathway in Drosophila host defense against pathogenic bacteria and fungi
    Jianming Chen
    Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China
    Proc Natl Acad Sci U S A 107:20774-9. 2010
    ..Together, our data demonstrate that the p38 pathway-mediated stress response contribute to Drosophila host defense against microbial infection...
  96. ncbi Role of mitogen-activated protein kinase kinase kinases in signal integration
    B D Cuevas
    Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7365, USA
    Oncogene 26:3159-71. 2007
    ..In this review, we describe how the MKKK 'hub' function regulates the specificity of MAPK activation, highlighting MKKKs as targets for therapeutic intervention in cancer and other diseases...
  97. pmc A new paradigm for MAPK: structural interactions of hERK1 with mitochondria in HeLa cells
    Soledad Galli
    Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany
    PLoS ONE 4:e7541. 2009
    ..This work indicates for the first time the presence of diverse ERK-complexes in mitochondria and thus provides a new perspective for assessing the functions of ERK1 in the regulation of cellular signalling and trafficking in HeLa cells...
  98. ncbi Advances in the development of cancer therapeutics directed against the RAS-mitogen-activated protein kinase pathway
    Judith S Sebolt-Leopold
    Oncovera Therapeutics, Ann Arbor, Michigan 48103, USA
    Clin Cancer Res 14:3651-6. 2008
    ....
  99. ncbi Role of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the secretion of tumor necrosis factor-alpha and interleukin-10 by the PPD antigen of Mycobacterium tuberculosis
    Saet Byel Jung
    Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, South Korea
    J Clin Immunol 25:482-90. 2005
    ..Collectively, these data suggest that the PI 3-K and MAPK pathways play a central role in the regulation of both pro- and anti-inflammatory cytokines by the PPD antigen of M. tuberculosis...
  100. ncbi Mitotic aberration coupled with centrosome amplification is induced by hepatitis B virus X oncoprotein via the Ras-mitogen-activated protein/extracellular signal-regulated kinase-mitogen-activated protein pathway
    Chawon Yun
    Department of Biochemistry and Molecular Biology, Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, South Korea
    Mol Cancer Res 2:159-69. 2004
    ..These findings may provide a possible mechanism by which HBx promotes phenotypic progression by predisposing chromosomal alteration in HBV-infected liver...
  101. pmc The unfolded protein response is induced by the cell wall integrity mitogen-activated protein kinase signaling cascade and is required for cell wall integrity in Saccharomyces cerevisiae
    Thomas Scrimale
    Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Mol Biol Cell 20:164-75. 2009
    ..We propose that the cellular responses to ER and cell wall stress are coordinated to buffer the cell against these two related cellular stresses...

Research Grants67

  1. MECHANISMS OF HEMORRHAGE AND EDEMA IN TPA STROKE THERAPY
    ENG LO; Fiscal Year: 2006
    ..This proposal should fit the goals of the Stroke PRG because it examines novel mechanisms that link tPA, cell signaling, MMPs, and hemorrhagic transformation in the neurovascular unit. ..
  2. STRETCH-INDUCED CYCLOOXYGENASE-2 IN UROTHELIAL CELLs
    Stephen Nakada; Fiscal Year: 2005
    ..abstract_text> ..
  3. Signaling Pathways in Pathogenesis of Renal Fibrosis
    JOSEPH GRANDE; Fiscal Year: 2004
    ..If successful, these interventions may retard progression of tissue injury to end-stage disease. ..
  4. Signaling Mechanisms of TCDD-induced AHR Activation
    Ying Xia; Fiscal Year: 2007
    ..abstract_text> ..
  5. NLR signaling in colitis and colorectal tumorigenesis
    Thirumala Devi Kanneganti; Fiscal Year: 2013
    ....
  6. Interactions and Dual Phosphorylation in MAP Kinase Cascades
    Elizabeth J Goldsmith; Fiscal Year: 2010
    ..Bisubstrate inhibitors, ATP-pTyr- peptide and ATP-pThr-peptide mimetics have been synthesized (by published chemistry) that will be used for crystallographic analysis bound to the MAP2K MEK6. ..
  7. Muller glia and neuronal regeneration in the retina
    Andy Fischer; Fiscal Year: 2009
    ..This information could be applied to not only stimulate neural regeneration to treat sight-threatening diseases of the retina, but also to control gliosis that may be detrimental to the pathogenesis of retinal disorders. ..
  8. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  9. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  10. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  11. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  12. Plasminogen activators and cerebral ischemic injury
    William M Armstead; Fiscal Year: 2010
    ....
  13. POTASSIUM CHANNELS AND CEREBRAL HEMODYNAMICS AFTER BRAIN
    William Armstead; Fiscal Year: 2005
    ..These studies may lead to therapies for brain injured children. ..
  14. HIV PROTEASE INHIBITORS EFFECT--NENDOTHELIAL DYSFUNCTION
    Changyi Chen; Fiscal Year: 2004
    ..Together, the integrated basic science, non-human primate and human investigations offer a multi disciplinary approach to the understanding and prevention of protease inhibitor-associated vascular complications. ..
  15. MLK3 function in neurofibromatosis tumor cells
    John Kyriakis; Fiscal Year: 2009
    ..Alternatively, merlin could repress the recruitment of MLK3 by Rho family GTPases. In Aim 3, we will use biochemical and molecular biological methods to explore these possibilities. ..
  16. Overcoming DC defects in cancer patients by VEGF trap
    Jeffrey Sosman; Fiscal Year: 2005
    ..Thereby, the correlative studies described here may lead to the establishment of VEGF inhibition, VEGF Trap, specifically, as an approach to combine with and enhance cancer immunotherapy. ..
  17. DIETARY NUTRIENTS AS MODULATORS OF HEPATIC METABOLISM
    Michael Pagliassotti; Fiscal Year: 2001
    ..Finally, to explain the decreased Km of G-6Pase for G6P during HS diet, and increased Vmax during HF diet, kinetics of this enzyme will be measured in the intact and disrupted microsomes. ..
  18. Role of SNAG Corepressors in Repression and Oncogenesis
    Kasirajan Ayyanathan; Fiscal Year: 2006
    ..abstract_text> ..
  19. Fourteenth Ovarian Workshop
    John Davis; Fiscal Year: 2002
    ..New investigators will be invited to submit expanded abstracts that will be evaluated for scientific merit and competition for travel awards and the Cornelia P. Channing New Investigator Award. ..
  20. Examination of activating Met mutations in tumorigenesis
    Carrie Graveel; Fiscal Year: 2007
    ..abstract_text> ..
  21. UNDERSTANDING STATUS EPILEPTICUS
    Jaideep Kapur; Fiscal Year: 2002
    ..4) Characterize the detailed pharmacological properties of dentate granule cell GABARs following SE. ..
  22. Control of embryonic stem cell self-renewal by Myc transcription factors
    Stephen Dalton; Fiscal Year: 2010
    ..The following hESC lines from the NIH Human Embryonic Stem Cell Registry will be used in these studies;BG01, TEO3 and WAO1. ..
  23. Molecular Mechanisms of PAR1 Downregulation
    JoAnn Trejo; Fiscal Year: 2005
    ..Thus we will use the C-tail of PAR1 as a probe in protein-protein interaction based strategies to identify new molecules that recognize and sort PAR1 to lysosomes...
  24. TRAINING IN AGE-RELATED NEURODEGENERATIVE DISEASES
    Elliott Mufson; Fiscal Year: 2008
    ..Finally the program will provide a broad-base of knowledge on neurodegenerative disorders as well as other instruction important for enhancing the interpersonal and professional skills of our trainees. ..
  25. ANGIOTENSIN AND CENTRAL NEUROHUMORAL ACTIVATION IN CHF
    Robert Felder; Fiscal Year: 2005
    ..This work will provide new information concerning the role of the central nervous system in the pathophysiology of CHF and will draw attention to the possibility of CNS directed drug therapy for heart failure. ..
  26. Genetic effectors of TGF-beta induced growth and arrest.
    BEN H PARK; Fiscal Year: 2010
    ..Isolated genes will be verified and validated by restoration of the putative gene and correlated with immunohistochemical studies using tissue microarrays. ..
  27. STUDY OF REG RECEPTOR-LIGAND BIOLOGY IN GI MUCOSA
    Brian Dieckgraefe; Fiscal Year: 2008
    ..These studies will also provide new insight into the role of Reg IV antagonists and lay the groundwork for development of therapeutic reagents active in gastrointestinal adenocarcinomas. ..
  28. NUTRIENT EFFECTS ON INSULIN ACTION
    Michael Pagliassotti; Fiscal Year: 2009
    ..abstract_text> ..
  29. Nongenomic Signaling Mechanisms of Environmental Estrogens
    Cheryl S Watson; Fiscal Year: 2011
    ..breast and pituitary cancers, infertility) must be understood so that exposures can be limited to safe levels. ..
  30. PPAR gamma Signaling and Lung Fibroblast Transdifferentiation
    Virender Rehan; Fiscal Year: 2009
    ..abstract_text> ..
  31. THE STRESS-ACTIVATED PROTEIN KINASE PATHWAY
    John M Kyriakis; Fiscal Year: 2010
    ..These studies will provide important details of a previously unknown signaling pathway required for inflammatory responses. ..
  32. Pathogenic Mechanisms of Shiga Toxins
    Vernon L Tesh; Fiscal Year: 2010
    ..An improved understanding of how these toxins cause disease is necessary to formulate effective therapeutic agents to block disease progression. ..
  33. Inhibition of nf-kb signaling in melanoma therapy
    Jeffrey Sosman; Fiscal Year: 2005
    ..Abstract Not Provided ..
  34. QSTAR ELITE PRO HIGH PERFORMANCE QUADRUPOLE TIME-OF-FLIGHT MASS SPECTROMETER
    Lin Yan; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  35. Signal Transduction Mechanisms in Neuroendocrine Neurons
    Arshad Khan; Fiscal Year: 2006
    ..This training will further my career goal of studying cellular signaling using an in vivo approach. ..
  36. Mentored Patient-Oriented Research Career Development Aw
    Zhenqi Liu; Fiscal Year: 2004
    ....
  37. Fifteenth Ovarian Workshop
    John Davis; Fiscal Year: 2004
    ..New investigators will be invited to submit expanded abstracts that will be evaluated for scientific merit and competition for travel awards and the Cornelia P. Channing New Investigator Award. ..
  38. Action of Novel Anti-tumor Agents on Cell Communication
    Diane Matesic; Fiscal Year: 2005
    ..abstract_text> ..
  39. TRANSMURAL SR REGULATION IN LV HYPERTROPHY
    Dorothy Vatner; Fiscal Year: 2003
    ..abstract_text> ..
  40. Pitt-SDM Research Infrastructure Improvement Intiative
    Mary Marazita; Fiscal Year: 2003
    ..As the IIP is developed, potential collaborations with other components of the University of Pittsburgh will be also examined. ..
  41. BETA-ADRENERGIC SIGNALING, DENERVATION AND HEART FAILURE
    Dorothy Vatner; Fiscal Year: 2002
    ..Secondly, no study has systematically examined catecholamine desensitization mechanisms using a combination of in vivo studies and isolated myocytes for transmural physiology, biochemistry and molecular biology. ..
  42. GENE MAPPING STUDIES OF ORAL/FACIAL CLEFTS--CHINA/INDIA
    Mary Marazita; Fiscal Year: 2002
    ....
  43. EXERCISE AND SKELETAL MUSCLE FATTY ACID METABOLISM
    LORRAINE TURCOTTE; Fiscal Year: 2002
    ..For the first time, malonyl-CoA levels will be correlated to the rate of fatty acid oxidation in skeletal muscle. ..
  44. IGF-I SIGNALING IN GRANULOSA CELLS
    John Davis; Fiscal Year: 2004
    ..This new insight may uncover mechanistic defects that underlay disorders of folliculogenesis, premature ovarian failure and disorders such as polycystic ovarian syndrome. ..
  45. Role of Egr-1 in Corpus Luteum Function
    John Davis; Fiscal Year: 2006
    ..abstract_text> ..
  46. MECHANISMS OF FIBER CARCINOGENESIS
    TOM HEI; Fiscal Year: 2001
    ..Cytogenetic and molecular alterations at the gene level will be analyzed from tumors and intermediate transformation stages to provide a mechanistic basis for tumor induction by mineral fibers. ..
  47. INHIBITION OF IFN GAMMA SIGNALING BY MYCOBACTERIA
    William Lafuse; Fiscal Year: 2004
    ..avium infected macrophages. 4) To determine the role of SOCS-3 in the inhibition of IFN-g signaling in M. avium infected macrophages. ..
  48. Oxidative Stress and ERK Signaling in AC-5 KO Longevity
    Dorothy Vatner; Fiscal Year: 2006
    ..Finding molecular switches, such as the one described in this project, could ameliorate disability with aging and would be a major step forward. [unreadable] [unreadable] [unreadable]..
  49. MECHANISMS OF ARSENIC CARCINOGENESIS
    TOM HEI; Fiscal Year: 2005
    ..abstract_text> ..
  50. Environmental Estrogens Acting via a Membrane Receptor
    CHERYL WATSON; Fiscal Year: 2004
    ..abstract_text> ..
  51. Regulation of Pulmonary Host Defense by Leptin
    Peter Mancuso; Fiscal Year: 2010
    ..They will also test the use of exogenous leptin as an adjunctive therapeutic agent in the treatment of pneumococcal pneumonia. ..
  52. REGULATION OF LUNG SURFACTANT PROTEIN B GENE EXPRESSION
    Vijayakumar Boggaram; Fiscal Year: 2006
    ..Such information may facilitate the development of newer therapies to treat lung dysfunction due to SP-B deficiency that occurs under conditions of elevated nitric oxide production in the lung. ..
  53. Genotype and Phenotype of Familial Nephropathy with Gout
    Mary Marazita; Fiscal Year: 2005
    ..abstract_text> ..
  54. Age and Gender Differences in Apoptosis and Stem Cells
    Dorothy Vatner; Fiscal Year: 2008
    ..In summary, this proposal will provide new conceptual information on gender differences with regard to compensatory adaptive mechanisms in the aging heart in a novel primate model. ..
  55. Dysregulation of AT, receptor in Transgenic Rats
    MICHELLE CLARK; Fiscal Year: 2004
    ..abstract_text> ..
  56. Planning International Orofacial Cleft Genetic Studies
    Mary Marazita; Fiscal Year: 2007
    ..g. power studies and sample size targets, research protocol and instruments), and will prepare the final research plan and submit a grant proposal to carry out the research project. [unreadable] [unreadable] [unreadable]..
  57. THE MUTAGENICITY OF MINERAL FIBERS
    TOM HEI; Fiscal Year: 2006
    ..By using specific DNA probes of other genes that have been regionally mapped to various sites on chromosome 11, the molecular spectrum of mutations induced by either asbestos or glass fiber control will be compared. ..
  58. Activation of Sickle Red Cell Adhesion
    Rahima Zennadi; Fiscal Year: 2006
    ..Overall, these experiments will elucidate the molecular mechanisms of LW-mediated SS RBC adhesion to endothelium and leukocytes, and thus how physiologic stress and stress hormones may contribute to vaso-occlusion. ..
  59. Antioxidant Defense System and Leydig Cell Aging
    Haolin Chen; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  60. Glutathione deficiency & immune dysfunction during aging
    Rui Ming Liu; Fiscal Year: 2006
    ....
  61. MECHANISMS OF TRANSFORMATION OF HEMATOPOIETIC CELLS
    JAMES MC CUBREY; Fiscal Year: 2001
    ..An understanding of how these signal transduction and apoptotic pathways impinge upon one another will further our comprehension of the consequences of abnormal oncogene activation and tumor progression. ..
  62. MOLECULAR ANALYSIS OF ANCHORING PROTEINS
    John Scott; Fiscal Year: 2003
    ....
  63. Molecular mechanism of ADNF and ADNP peptides in neuroprotection to alcohol
    Youssef Sari; Fiscal Year: 2008
    ..This data will shed light on the mechanisms governing brain ontogeny and will pave the path toward potential therapeutics against developmental insults associated with prenatal alcohol exposure. [unreadable] [unreadable] [unreadable]..
  64. Ras/Raf & PI3K/Akt Induced Breast Cancer Drug Resistance
    JAMES MC CUBREY; Fiscal Year: 2007
    ..Throughthese studies,moreinformationwillbe availableto treatbreast andothercancerpatientswithcombinationsof drugs,whichinhibitsignaltransductionand anti-apoptoticpathwaysleadingtodrug resistance. ..
  65. The Exocyst in Synthesis, Cystogenesis and Tubulogenesis
    JOSHUA LIPSCHUTZ; Fiscal Year: 2009
    ..abstract_text> ..
  66. Gene Expression Changes in Early 3D Renal Tubulogenesis
    JOSHUA LIPSCHUTZ; Fiscal Year: 2007
    ..unreadable] [unreadable]..