mitogen activated protein kinase 1

Summary

Summary: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.

Top Publications

  1. ncbi Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim
    Rebecca Ley
    Inositide Laboratory, Signalling Programme, The Babraham Institute, Cambridge CB2 4AT, United Kingdom
    J Biol Chem 278:18811-6. 2003
  2. ncbi Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory
    Cristina Mazzucchelli
    San Raffaele Research Institute and University, Via Olgettina 58, 20132 Milano, Italy
    Neuron 34:807-20. 2002
  3. 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
  4. ncbi Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation
    J M Brondello
    Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A Lacassagne, 33 Avenue de Valombrose, Nice 06189, France
    Science 286:2514-7. 1999
  5. ncbi The role of erk1 and erk2 in multiple stages of T cell development
    April M Fischer
    Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093 0377, USA
    Immunity 23:431-43. 2005
  6. ncbi How MAP kinases are regulated
    M H Cobb
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235 9041, USA
    J Biol Chem 270:14843-6. 1995
  7. ncbi The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation
    Y Chu
    Labortory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 271:6497-501. 1996
  8. ncbi Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments
    J Albanell
    Laboratory of Oncology Research, Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona, Spain
    Cancer Res 61:6500-10. 2001
  9. ncbi Raf-1 kinase is required for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload
    Ian S Harris
    Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA
    Circulation 110:718-23. 2004
  10. ncbi Atomic structure of the MAP kinase ERK2 at 2.3 A resolution
    F Zhang
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas
    Nature 367:704-11. 1994

Research Grants

Detail Information

Publications277 found, 100 shown here

  1. ncbi Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim
    Rebecca Ley
    Inositide Laboratory, Signalling Programme, The Babraham Institute, Cambridge CB2 4AT, United Kingdom
    J Biol Chem 278:18811-6. 2003
    ..Our findings provide new insights into the regulation of Bim and the role of the ERK pathway in cell survival...
  2. ncbi Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory
    Cristina Mazzucchelli
    San Raffaele Research Institute and University, Via Olgettina 58, 20132 Milano, Italy
    Neuron 34:807-20. 2002
    ..Our results reveal an unexpected complexity of ERK-dependent signaling in the brain and a critical regulatory role for ERK1 in the long-term adaptive changes underlying striatum-dependent behavioral plasticity and drug addiction...
  3. 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...
  4. ncbi Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation
    J M Brondello
    Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A Lacassagne, 33 Avenue de Valombrose, Nice 06189, France
    Science 286:2514-7. 1999
    ..These results illustrate the importance of regulated protein degradation in the control of mitogenic signaling...
  5. ncbi The role of erk1 and erk2 in multiple stages of T cell development
    April M Fischer
    Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093 0377, USA
    Immunity 23:431-43. 2005
    ..Erk activity is essential for the process of positive selection, and it differentially affects CD4 and CD8 T cell maturation; yet, diminished expression itself is not sufficient to alter lineage commitment...
  6. ncbi How MAP kinases are regulated
    M H Cobb
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235 9041, USA
    J Biol Chem 270:14843-6. 1995
  7. ncbi The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation
    Y Chu
    Labortory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 271:6497-501. 1996
    ..A hyperactive allele of ERK2 (D319N), analogous to the Drosophila sevenmaker gain-of-function mutation, has significantly reduced sensitivity to all three MAP kinase phosphatases in vivo...
  8. ncbi Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments
    J Albanell
    Laboratory of Oncology Research, Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona, Spain
    Cancer Res 61:6500-10. 2001
    ..The inhibition of ERK1/2 activation in vitro and in vivo by compounds targeting the EGF receptor points to the interest of ERK1/2 as potential surrogate markers of EGF-receptor signaling in clinical therapeutic studies...
  9. ncbi Raf-1 kinase is required for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload
    Ian S Harris
    Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA
    Circulation 110:718-23. 2004
    ..Mechanical stress in the heart results in the activation of the small GTPase ras and the Raf-1/MEK/ERK signaling cascade in addition to other signaling pathways...
  10. ncbi Atomic structure of the MAP kinase ERK2 at 2.3 A resolution
    F Zhang
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas
    Nature 367:704-11. 1994
    ..Activation of ERK2 is thus likely to involve both global and local conformational changes...
  11. pmc The Erk2 MAPK regulates CD8 T cell proliferation and survival
    Warren N D'Souza
    Department of Cellular and Molecular Medicine, Division of Biological Science, Molecular Biology Section, University of California, San Diego, La Jolla, CA 92093, USA
    J Immunol 181:7617-29. 2008
    ..These studies ascribe multifaceted functions specific to Erk2 in CD8 T cell activation, proliferation, and survival...
  12. pmc The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice
    O F Bueno
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    EMBO J 19:6341-50. 2000
    ..The results of the present study indicate that the MEK1-ERK1/2 signaling pathway stimulates a physiologic hypertrophy response associated with augmented cardiac function and partial resistance to apoptotsis...
  13. pmc Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3
    Sijiu Liu
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA
    Proc Natl Acad Sci U S A 103:5326-31. 2006
    ..The results establish a structural model for understanding how MAP kinases interact with their regulators and substrates and provide new insights into how MAP kinase docking specificity can be achieved...
  14. ncbi ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF
    T G Boulton
    Department of Pharmacology, University of Texas Southwestern Graduate School of Biomedical Sciences, Dallas 75235 9041
    Cell 65:663-75. 1991
    ..Individual family members may mediate responses in different developmental stages, in different cell types, or following exposure to different extracellular signals...
  15. pmc The MAPK(ERK-1,2) pathway integrates distinct and antagonistic signals from TGFalpha and FGF7 in morphogenesis of mouse mammary epithelium
    Jimmie E Fata
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Dev Biol 306:193-207. 2007
    ..Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK(ERK1,2) activation...
  16. ncbi PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase
    E Formstecher
    INSERM U114, College de France, Paris
    Dev Cell 1:239-50. 2001
    ..Thus, PEA-15 can redirect the biological outcome of MAP kinase signaling by regulating the subcellular localization of ERK MAP kinase...
  17. ncbi Different accumulation of activated extracellular signal-regulated kinases (ERK 1/2) and role in cell-cycle alterations by epidermal growth factor, hydrogen peroxide, or asbestos in pulmonary epithelial cells
    S Buder-Hoffmann
    Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
    Am J Respir Cell Mol Biol 24:405-13. 2001
    ..Our results suggest that ERKs mediate cell-cycle alterations during the development of epithelial cell apoptosis or proliferation by diverse ERK stimuli...
  18. pmc Extracellular signal-regulated kinase 2 is necessary for mesoderm differentiation
    Yao Yao
    Department of Biology, Vertex Pharmaceuticals, 130 Waverly Street, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 100:12759-64. 2003
    ..These data indicate that ERK2 plays an essential role in mesoderm differentiation during embryonic development...
  19. ncbi Extracellular signaling-regulated kinase-1 and -2 (ERK 1/2) mediate referred hyperalgesia in a murine model of visceral pain
    Alba Galan
    Department of Physiology, University of Alcala, Alcala de Henares, E 28871 Madrid, Spain
    Brain Res Mol Brain Res 116:126-34. 2003
    ..The time course and subcellular localization of the effects observed suggest that ERK is involved in transcriptional events underlying the maintenance of secondary hyperalgesia...
  20. ncbi Maintenance of differentiated phenotype of articular chondrocytes by protein kinase C and extracellular signal-regulated protein kinase
    Young Mee Yoon
    National Research Laboratory, Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500 712, Korea
    J Biol Chem 277:8412-20. 2002
    ....
  21. ncbi Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient
    Marcin Wysoczynski
    Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, KY 40202, USA
    Blood 105:40-8. 2005
    ....
  22. ncbi Characterization of a novel cell line established from a patient with Herceptin-resistant breast cancer
    Minna Tanner
    Laboratory of Cancer Biology, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland
    Mol Cancer Ther 3:1585-92. 2004
    ..Erk1/2 phosphorylation was slightly reduced but still evident in JIMT-1 cells. We conclude that the JIMT-1 cell line provides a valuable experimental model for studies of new trastuzumab-resistance mechanisms...
  23. ncbi Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke
    Nik Sawe
    Department of Neurosurgery and Stanford Stroke Center, Stanford University, Stanford, California 94305 5327, USA
    J Neurosci Res 86:1659-69. 2008
    ..Future experiments should be conducted to optimize the protective effect of ERK1/2 while blocking its detrimental actions...
  24. ncbi Gadd45a and Gadd45b protect hematopoietic cells from UV-induced apoptosis via distinct signaling pathways, including p38 activation and JNK inhibition
    Mamta Gupta
    Fels Institute of Cancer Research and Molecular Biology and Department of Biochemistry, Temple University School of Medicine, 3307 N Broad Street, Philadelphia, PA 19140, USA
    J Biol Chem 281:17552-8. 2006
    ....
  25. ncbi Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F
    K Shide
    Department of Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, Kiyotake, Miyazaki, Japan
    Leukemia 22:87-95. 2008
    ..We conclude that in vivo expression of JAK2 V617F results in ET-, PMF- and PV-like disease...
  26. ncbi Regulation of Cdc25C by ERK-MAP kinases during the G2/M transition
    Ruoning Wang
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cell 128:1119-32. 2007
    ..Inhibition of ERK activation partially inhibits T48 phosphorylation, Cdc25C activation, and mitotic induction. These findings demonstrate that ERK-MAP kinases are directly involved in activating Cdc25 during the G(2)/M transition...
  27. ncbi ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status
    Song Ja Kim
    National Research Laboratory, Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500 712, Korea
    J Biol Chem 277:1332-9. 2002
    ..Our findings collectively suggest that ERK-1/2 and p38 kinase oppositely regulate NO-induced apoptosis of chondrocytes, in association with p53 accumulation, caspase-3 activation, and differentiation status...
  28. pmc Epidermal growth factor receptor and protein kinase C signaling to ERK2: spatiotemporal regulation of ERK2 by dual specificity phosphatases
    Christopher J Caunt
    Laboratories for Integrated Neuroscience and Endocrinology, Department of Clinical Sciences at South Bristol, University of Bristol, Whitson Street, Bristol, U K
    J Biol Chem 283:6241-52. 2008
    ..These mutations also impaired the ability of ERK2-GFP to bind DUSP2 and -4. Together, our data reveal a novel, stimulus-specific, and phosphatase-specific mechanism of ERK2 regulation in the nucleus by DUSP1, -2, and -4...
  29. ncbi Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma
    M Lopez-Ilasaca
    Max Planck Research Unit Molecular Cell Biology, Medical Faculty, University of Jena, 07747 Jena, Germany
    Science 275:394-7. 1997
    ..Signaling from PI3Kgamma to MAPK appears to require a tyrosine kinase, Shc, Grb2, Sos, Ras, and Raf. These findings indicate that PI3Kgamma mediates Gbetagamma-dependent regulation of the MAPK signaling pathway...
  30. ncbi p44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1)-dependent signaling contributes to epithelial skin carcinogenesis
    Christine Bourcier
    Institute of Signaling, Developmental Biology and Cancer Research, UMR Centre National de la Recherche Scientifique, Nice, France
    Cancer Res 66:2700-7. 2006
    ..These results highlight the importance of ERK1 in skin homeostasis and in the process of skin tumor development...
  31. ncbi Extracellular signal-regulated kinase-dependent proliferation is mediated through the protein kinase A/B-Raf pathway in human uveal melanoma cells
    Armelle Calipel
    INSERM U598 and IFR58, Institut Biomedical des Cordeliers, Paris 75006, France
    J Biol Chem 281:9238-50. 2006
    ..Altogether, our results suggest that the PKA/B-Raf pathway is a potential target for therapeutic strategies against (WT)B-Raf-expressing uveal melanoma...
  32. ncbi Rho GTPases are over-expressed in human tumors
    G Fritz
    Institute of Toxicology, Division of Applied Toxicology, University of Mainz, Germany
    Int J Cancer 81:682-7. 1999
    ..Overall, increase in the amount of Rho GTPases, in particular RhoA, appears to be a frequent event in different types of human tumors. This supports the view that Rho GTPases are involved in human carcinogenesis...
  33. ncbi Hyperactivation of MAPK induces loss of ERalpha expression in breast cancer cells
    A S Oh
    Lombardi Cancer Center, Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA
    Mol Endocrinol 15:1344-59. 2001
    ....
  34. ncbi Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice
    G Pages
    Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France
    Science 286:1374-7. 1999
    ..The p44 MAPK apparently has a specific role in thymocyte development...
  35. pmc Specific inactivation and nuclear anchoring of extracellular signal-regulated kinase 2 by the inducible dual-specificity protein phosphatase DUSP5
    Margret Mandl
    Cancer Research UK, Molecular Pharmacology Unit, Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, United Kingdom
    Mol Cell Biol 25:1830-45. 2005
    ..In addition, our data indicate that the cytoplasm may not be an exclusive site of MAP kinase activation...
  36. ncbi IL-1beta-stimulated activation of ERK1/2 and p38alpha MAPK mediates the transcriptional up-regulation of IL-6, IL-8 and GRO-alpha in HeLa cells
    Huei Ting Yang
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, United Kingdom
    Cell Signal 20:375-80. 2008
    ....
  37. ncbi Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis
    Yasunari Mizumoto
    Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kanazawa University, 13 1, Takaramachi, Kanazawa, Ishikawa 920 8641, Japan
    Cancer Sci 98:652-8. 2007
    ..047). These findings suggest that ERK activation occurs in a KRAS- and BRAF-independent manner in endometrial cancer, and is associated with favorable prognosis...
  38. 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...
  39. ncbi The anti-apoptotic protein PEA-15 is a tight binding inhibitor of ERK1 and ERK2, which blocks docking interactions at the D-recruitment site
    Kari Callaway
    Graduate Program in Biochemistry, University of Texas at Austin, Texas 78712, USA
    Biochemistry 46:9187-98. 2007
    ..Therefore, in addition to sequestering ERK1/2 in the cytoplasm, PEA-15 has the potential to modulate the activity of ERK2 in cells by competing directly with proteins that contain D-sites...
  40. ncbi Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells
    D C Márquez
    Department of Medicine, Division of Hematology Oncology, UCLA School of Medicine, Los Angeles, California, 90095 1678, USA
    Oncogene 20:5420-30. 2001
    ..Thus, membrane-associated forms of estrogen receptor may play a role in promoting intracellular signaling for hormone-mediated proliferation and survival of breast cancers and offer a new target for antitumor therapy...
  41. pmc Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor
    S Wennström
    Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
    Mol Cell Biol 19:4279-88. 1999
    ....
  42. ncbi ERK activation propagates in epithelial cell sheets and regulates their migration during wound healing
    Yutaka Matsubayashi
    Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Curr Biol 14:731-5. 2004
    ..Thus, our results identify specific requirements of ERK1/2 MAP kinase for epithelial cell sheet movement...
  43. ncbi ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell migration: a comparison between mesothelioma and mesothelial cells
    Jun Zhong
    Department of Pharmacology, The Woolcock Institute of Medical Research, University of Sydney, New South Wales, Australia
    J Cell Physiol 207:540-52. 2006
    ..Mesothelioma progression depends on an interaction with mesothelial cells that provide MT1-MMP necessary to activate pro-MMP-2 to facilitate migration through an extracellular matrix (ECM) layer...
  44. ncbi Mitogen-activated protein kinases and cerebral ischemia
    K Nozaki
    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Japan
    Mol Neurobiol 23:1-19. 2001
    ....
  45. ncbi Mechanisms regulating the constitutive activation of the extracellular signal-regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of ribonucleic acid interference for ERK1/2 on cancer cell proliferation
    Rosemary Steinmetz
    Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana 46202, USA
    Mol Endocrinol 18:2570-82. 2004
    ..These results provide evidence that the ERK pathway plays a major role in ovarian cancer pathogenesis and that down-regulation of this master signaling pathway is highly effective for the inhibition of ovarian tumor growth...
  46. ncbi Role of Raf in vascular protection from distinct apoptotic stimuli
    Alireza Alavi
    Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 301:94-6. 2003
    ..These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis...
  47. ncbi Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells
    J Huot
    Centre de recherche en cancérologie de l Université Laval, L Hôtel Dieu de Québec, Canada
    Circ Res 80:383-92. 1997
    ..Consequently, the p38 MAP kinase pathway may participate in the several oxyradical-activated functions of the endothelium that are associated with reorganization of microfilament network...
  48. ncbi Cyclophilin A is required for CXCR4-mediated nuclear export of heterogeneous nuclear ribonucleoprotein A2, activation and nuclear translocation of ERK1/2, and chemotactic cell migration
    Heng Pan
    Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    J Biol Chem 283:623-37. 2008
    ..Finally, CXCL12-induced chemotaxis of HEK293 cells stably expressing CXCR4 or Jurkat T cells was inhibited by CyPA RNAi or CsA treatment...
  49. pmc Interstitial flow induces MMP-1 expression and vascular SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism
    Zhong Dong Shi
    City College of New York, City University of New York, Department of Biomedical Engineering, New York, NY 10031, USA
    Am J Physiol Heart Circ Physiol 298:H127-35. 2010
    ....
  50. pmc High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome
    Klaus Jürgen Schmitz
    Institute of Pathology, University Hospital of Essen Duisburg, Essen, Germany
    Breast Cancer Res 7:R194-203. 2005
    ..In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy...
  51. ncbi Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase
    K L Guan
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    J Biol Chem 270:7197-203. 1995
    ..HVH2 mRNA showed an expression pattern distinct from CL100 (human homologue of mouse MKP1) and PAC1, two previously identified MAP kinase phosphatases. Our data suggest a possible role of HVH2 in MAP kinase regulation...
  52. ncbi The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases
    V Volmat
    Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre Antoine Lacassagne, 06189 Nice, France
    J Cell Sci 114:3433-43. 2001
    ..Hence, the nucleus is a critical site for mitogenic signal termination by: (1) nuclear sequestration of p42/p44 MAPKs away from MEK, their cytoplasmic activator; and (2) dephosphorylation by specific nuclear phosphatases...
  53. ncbi The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway
    Alice J Chen
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 277:36592-601. 2002
    ..Taken together, these studies identify a positive regulator for the JNK pathway and suggest a novel role for DSP in mitogen-activated protein kinase regulation...
  54. ncbi Role of ERK and JNK pathways in regulating cell motility and matrix metalloproteinase 9 production in growth factor-stimulated human epidermal keratinocytes
    M E Zeigler
    Department of Pathology, The University of Michigan Medical School, Ann Arbor, USA
    J Cell Physiol 180:271-84. 1999
    ..This evidence suggests that while ERK and JNK activity are necessary for AP-1 activation, ERK but not JNK is sufficient in stimulating cell motility...
  55. pmc Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters
    Barbara Kroczynska
    Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA
    Proc Natl Acad Sci U S A 103:14128-33. 2006
    ..Our results indicate that mineral fibers and viruses can be cocarcinogens and suggest that lower amounts of asbestos may be sufficient to cause MM in individuals infected with SV40...
  56. ncbi The SDF-1-CXCR4 axis stimulates VEGF secretion and activates integrins but does not affect proliferation and survival in lymphohematopoietic cells
    J Kijowski
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Stem Cells 19:453-66. 2001
    ..We conclude that perturbation of the SDF-1-CXCR4 axis during HIV infection may affect interactions of hematopoietic cells with the hematopoietic microenvironment...
  57. ncbi Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK
    T McKinnon
    Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 5C1
    J Clin Endocrinol Metab 86:3665-74. 2001
    ..These results, taken together, reveal that IGF-II stimulates extravillous trophoblast cell migration by signaling through IGF type 2 receptor, involving inhibitory G proteins and activating the MAPK pathway...
  58. pmc LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans
    Myon Hee Lee
    Howard Hughes Medical Institute, University of Wisconsin Madison, Madison, WI 53706, USA
    EMBO J 25:88-96. 2006
    ..The control of germline proliferation by LIP-1 has intriguing parallels with the control of stem cells and progenitor cells in vertebrates...
  59. pmc Rapid effects of retinoic acid on CREB and ERK phosphorylation in neuronal cells
    Estela Cañón
    Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas and Universidad Autonoma de Madrid, 28029 Madrid, Spain
    Mol Biol Cell 15:5583-92. 2004
    ..These results demonstrate that RA, by a nongenomic mechanism, stimulates signaling pathways that lead to phosphorylation of transcription factors, which in turn activate the transcription of genes involved in neuronal differentiation...
  60. ncbi Fluid shear stress activation of focal adhesion kinase. Linking to mitogen-activated protein kinases
    S Li
    Department of Bioengineering and Institute for Biomedical Engineering, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 272:30455-62. 1997
    ..These results demonstrate that FAK signaling is critical in the shear stress-induced dual activation of ERK and JNK...
  61. ncbi Molecular interpretation of ERK signal duration by immediate early gene products
    Leon O Murphy
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Nat Cell Biol 4:556-64. 2002
    ..Together, our data identify a general mechanism by which cells can interpret differences in ERK activation kinetics...
  62. ncbi MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells
    J S Arthur
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    FEBS Lett 482:44-8. 2000
    ..Thus MSK1 is required for CREB and ATF1 phosphorylation after mitogenic stimulation of ES cells...
  63. ncbi A role for the MEK/MAPK pathway in PMA-induced cell cycle arrest: modulation of megakaryocytic differentiation of K562 cells
    R Herrera
    Department of Cell Biology, Parke Davis Pharmaceutical Research Division of Warner Lambert Company, Ann Arbor, Michigan 48105, USA
    Exp Cell Res 238:407-14. 1998
    ....
  64. ncbi Adhesion-dependent activation of the ERK1/2 cascade is by-passed in melanoma cells
    Sean R Conner
    Center for Cell Biology and Cancer Research, Albany Medical College, Albany, New York 12208, USA
    J Biol Chem 278:34548-54. 2003
    ..These results indicate that alterations in the adhesion requirement for ERK1/2 signaling in melanocytes are associated with the acquisition of malignant cell behavior...
  65. pmc Interleukin-1beta mediates human airway epithelial cell migration via NF-kappaB
    Steven R White
    Univ of Chicago, Section of Pulmonary and Critical Care Medicine, 5841 S Maryland Ave, MC 6076, Chicago, IL 60637, USA
    Am J Physiol Lung Cell Mol Physiol 295:L1018-27. 2008
    ....
  66. ncbi Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells
    Valerie E Meyers
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Cell Biochem 93:697-707. 2004
    ..Taken together, our findings indicate that MMG decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis...
  67. pmc Spatiotemporal regulation of ERK2 by dual specificity phosphatases
    Christopher J Caunt
    Laboratory for Integrated Neuroscience and Endocrinology, Department of Clinical Sciences at South Bristol, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom
    J Biol Chem 283:26612-23. 2008
    ..Together with the known tissue-specific expression of DUSPs and the importance of ERK1/2 in cell regulation, our data support the potential value of DUSPs as targets for drug therapy...
  68. ncbi BCR/ABL kinase inhibition by imatinib mesylate enhances MAP kinase activity in chronic myelogenous leukemia CD34+ cells
    Su Chu
    Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA
    Blood 103:3167-74. 2004
    ..These mechanisms may contribute to incomplete elimination of CML progenitors by imatinib...
  69. pmc Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth
    Bastiano Sanna
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC7020, Cincinnati, OH 45229 3039, USA
    Mol Cell Biol 25:865-78. 2005
    ..Collectively, these results indicate that calcineurin-NFAT and MEK1-ERK1/2 pathways constitute a codependent signaling module in cardiomyocytes that coordinately regulates the growth response through two distinct mechanisms...
  70. ncbi Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/EGR-1 and Ca(++)/NFAT
    Valery N Bochkov
    Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria
    Blood 99:199-206. 2002
    ..Thus, oxidized phospholipids may contribute to inflammation by activating pathways alternative to the classical NF-kappa B pathway...
  71. ncbi Extracellular signal-regulated kinases are involved in the acute activation of steroidogenesis in immature rat Leydig cells by human chorionic gonadotropin
    N Martinelle
    Department of Woman and Child Health, Pediatric Endocrinology Unit, Q2 08, Karolinska Institute and Hospital, Astrid Lindgren Children s Hospital, S 17176 Stockholm, Sweden
    Endocrinology 145:4629-34. 2004
    ....
  72. ncbi The RasGAP-binding protein p62dok is a mediator of inhibitory FcgammaRIIB signals in B cells
    I Tamir
    Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver 80206, USA
    Immunity 12:347-58. 2000
    ..Using chimeric FcgammaRIIB containing the RasGAP-binding domain of p62dok, we demonstrate that p62dok contains all structural information required to mediate the inhibitory effect of FcgammaRIIB on Erk activation...
  73. ncbi Upregulation of AT1 receptor gene on activation of protein kinase Cbeta/nicotinamide adenine dinucleotide diphosphate oxidase/ERK1/2/c-fos signaling cascade mediates long-term pressor effect of angiotensin II in rostral ventrolateral medulla
    Samuel H H Chan
    Center for Neuroscience, National Sun Yat Sen University, and Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China
    J Hypertens 25:1845-61. 2007
    ....
  74. ncbi Extracellularly regulated kinases 1/2 (p44/42 mitogen-activated protein kinases) phosphorylate synapsin I and regulate insulin secretion in the MIN6 beta-cell line and islets of Langerhans
    Christine Longuet
    Unité Institut National de la Santé et de la Recherche Médecale U376, Centre Hospitalier Universitaire Arnaud de Villeneuve, 371 rue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France
    Endocrinology 146:643-54. 2005
    ..Taken together, our results demonstrate new aspects of the glucose-dependent actions of ERK1/2 in beta-cells exerted on cytoplasmic proteins, including synapsin I, and participating in the overall glucose-induced insulin secretion...
  75. ncbi Constitutive ERK1/2 activation in esophagogastric rib bone marrow micrometastatic cells is MEK-independent
    O P Barry
    Cork Cancer Research Center, National University of Ireland, Cork, Ireland
    J Biol Chem 276:15537-46. 2001
    ..These findings have important implications for drug treatment strategies which currently target MEK in other forms of cancer...
  76. ncbi Phosphorylation of ERK1/2 mitogen-activated protein kinase is associated with poor response to anti-hormonal therapy and decreased patient survival in clinical breast cancer
    J M Gee
    Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Cardiff, United Kingdom
    Int J Cancer 95:247-54. 2001
    ....
  77. ncbi Epidermal growth factor-stimulated intestinal epithelial cell migration requires Src family kinase-dependent p38 MAPK signaling
    Mark R Frey
    Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2576, USA
    J Biol Chem 279:44513-21. 2004
    ....
  78. pmc Dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition of breast cancer cells
    D C Lev
    Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Br J Cancer 91:795-802. 2004
    ..However, inhibiting both EGFR/HER2 and MAPK signalling can result in significant growth inhibition and apoptosis of EGFR-expressing breast cancer cells...
  79. ncbi Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy
    Rama Pai
    Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, USA
    Nat Med 8:289-93. 2002
    ..Our findings that PGE2 transactivates EGFR reveal a previously unknown mechanism by which PGE2 mediates trophic actions resulting in gastric and intestinal hypertrophy as well as growth of colonic polyps and cancers...
  80. pmc Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB
    M Deak
    MRC Protein Phosphorylation Unit, Departments of Biochemistry, Anatomy and Physiology, University of Dundee, Scotland
    EMBO J 17:4426-41. 1998
    ..These findings, together with other observations, suggest that MSK1 may mediate the growth-factor and stress-induced activation of CREB...
  81. ncbi Prostaglandin E2 regulates angiogenesis via activation of fibroblast growth factor receptor-1
    Federica Finetti
    Department of Molecular Biology, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy
    J Biol Chem 283:2139-46. 2008
    ..This signaling pattern is similar to the autocrine-paracrine mechanism which operates in endothelial cells to support neovascular growth...
  82. ncbi Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes
    L M Luttrell
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 283:655-61. 1999
    ....
  83. ncbi Inhibition of ERK phosphorylation decreases nociceptive behaviour in monoarthritic rats
    Célia D Cruz
    Institute of Histology and Embryology, Faculty of Medicine and IBMC, University of Porto, Alameda Hernani Monteiro, 4200 319 Porto, Portugal
    Pain 116:411-9. 2005
    ..Taken together, these findings suggest that ERK phosphorylation in spinal cord neurones plays an important role in chronic inflammatory articular pain and that its inhibition may provide significant anti-nociception...
  84. ncbi Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF
    E J Filardo
    Department of Medicine and Surgery, Rhode Island Hospital and Brown University, Providence 02903, USA
    Mol Endocrinol 14:1649-60. 2000
    ..Our data imply that ER-negative breast tumors that continue to express GPR30 may use estrogen to drive growth factor-dependent cellular responses...
  85. ncbi ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia
    Chiara Gregorj
    Division of Hematology, Department of Cellular Biotechnologies and Hematology, University La Sapienza of Rome, Italy
    Blood 109:5473-6. 2007
    ..027). Effective approaches toward MEK inhibition need to be explored in order to evaluate whether this may represent a new therapeutic strategy for adult ALL patients...
  86. ncbi Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells
    Kazuya Terasawa
    Department of Pharmcogenomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo ku, Japan
    FEBS J 276:3269-76. 2009
    ..These results reveal that the ERK signal regulates miR-221/222 expression, and that these miRNAs might contribute to NGF-dependent cell survival in PC12 cells...
  87. ncbi A novel role for FAK as a protease-targeting adaptor protein: regulation by p42 ERK and Src
    Neil O Carragher
    The Beatson Institute for Cancer Research, Cancer Research United Kingdom, Beatson Laboratories, Glasgow G61 1BD, Scotland, United Kingdom
    Curr Biol 13:1442-50. 2003
    ..Furthermore, FAK is necessary for recruiting both Calpain 2 and p42ERK/MAPK to peripheral adhesion sites facilitating maximal Calpain activity...
  88. pmc Multiple functions and dynamic activation of MPK-1 extracellular signal-regulated kinase signaling in Caenorhabditis elegans germline development
    Min Ho Lee
    Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genetics 177:2039-62. 2007
    ....
  89. ncbi Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta
    Venkateshwar G Keshamouni
    Department of Pathology, Wayne State University, Detroit, Michigan 48201, USA
    J Biol Chem 277:22558-65. 2002
    ..This evaluation of downstream signaling revealed that E(2)-induced Erk activation is mediated by a HRG/HER-2/PKC-delta/Ras pathway that could be crucial for E(2)-dependent growth-promoting effects in early stages of tumor progression...
  90. ncbi p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells
    Mi Sung Kim
    College of Pharmacy, Duksung Women s University, Seoul 132 714, Korea
    Cancer Res 63:5454-61. 2003
    ..This study reveals the p38 kinase as a key signaling molecule differentially regulated by H-ras and N-ras, leading to H-ras-specific cell invasive and migrative phenotypes in human breast epithelial cells...
  91. ncbi Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the phosphatase catalytically
    P Chen
    Laboratory of Cellular and Molecular Biology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 276:29440-9. 2001
    ..Our studies provided a mechanistic explanation for the substrate preference of MKP-2 and suggest that catalytic activation of MKP-2 upon binding to its substrates is crucial for its function...
  92. ncbi Calcium-mediated interactions regulate the subcellular localization of extracellular signal-regulated kinases
    Dana Chuderland
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 283:11176-88. 2008
    ..Thus, calcium regulates ERK localization, which is important for the compartmentalization of ERKs with their proper substrates and thereby their signaling specificity...
  93. ncbi Involvement of ERK1/2 signaling pathway in DJ-1-induced neuroprotection against oxidative stress
    Li Gu
    Beijing Institute for Neuroscience, Capital Medical University CMU, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Youanmenwai Xitoutiao 10, Beijing 100069, China
    Biochem Biophys Res Commun 383:469-74. 2009
    ..Inhibition of the ERK1/2 signaling pathway with a MEK1/2 inhibitor reversed these changes. We conclude that DJ-1 does affect the ERK1/2 signaling pathway and change the susceptibility of cells to oxidative stress...
  94. ncbi GIT1 is a scaffold for ERK1/2 activation in focal adhesions
    Guoyong Yin
    Center for Cardiovascular Research and Department of Medicine, University of Rochester, Rochester, New York 14642, USA
    J Biol Chem 280:27705-12. 2005
    ..In summary, the present study further supports a key role for GIT1 (a MEK1-binding protein) as a scaffold for signal transduction in focal adhesions...
  95. ncbi Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases
    G T Kampen
    University of Texas Medical Branch, Department of Internal Medicine, Division of Allergy and Immunology, Galveston, TX 77555 0762, USA
    Blood 95:1911-7. 2000
    ..Blood. 2000;95:1911-1917)..
  96. ncbi Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase
    M Camps
    Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development S A, CH 1228 Plan les Ouates, Geneva, Switzerland
    Science 280:1262-5. 1998
    ..Catalytic activation of MAP kinase phosphatases through substrate binding may regulate MAP kinase activation by a large number of receptor systems...
  97. ncbi Using U0126 to dissect the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in the regulation of gene expression by endothelin-1 in cardiac myocytes
    Robert A Kennedy
    National Heart and Lung Institute NHLI Division, Faculty of Medicine, Imperial College London, Flowers Building Floor 4, UK
    J Mol Cell Cardiol 41:236-47. 2006
    ..Our data suggest that the majority of changes in gene expression induced by endothelin-1 are mediated by the ERK1/2 cascade...
  98. ncbi Essential role of calcium in vascular endothelial growth factor A-induced signaling: mechanism of the antiangiogenic effect of carboxyamidotriazole
    Martin Faehling
    Department of Internal Medicine II, University of Ulm, 89081 Ulm, Germany
    FASEB J 16:1805-7. 2002
    ..Calcium-dependent NO formation may represent a link between calcium signaling and proliferation...
  99. ncbi Ischemic postconditioning in pigs: no causal role for RISK activation
    Andreas Skyschally
    Institut fur Pathophysiologie, Universitatsklinikum Essen, Germany
    Circ Res 104:15-8. 2009
    ..In protocol 2, Wortmannin and U0126 blocked the increases in RISK phosphorylation during reperfusion, but infarct size was still smaller with IPoC (15+/-7%) than with IFR (35+/-6%; P<0.05)...
  100. ncbi ERK1/2 antagonizes glycogen synthase kinase-3beta-induced apoptosis in cortical neurons
    Michal Hetman
    Departments of Environmental Health and Pharmacology, University of Washington, Seattle, WA 98195 7234, USA
    J Biol Chem 277:49577-84. 2002
    ..Furthermore, ERK1/2 inhibits GSK3beta activity via a novel mechanism that is independent of Ser-9 phosphorylation and likely does not involve Tyr-216 phosphorylation...
  101. ncbi Thrombin suppresses endothelial nitric oxide synthase and upregulates endothelin-converting enzyme-1 expression by distinct pathways: role of Rho/ROCK and mitogen-activated protein kinase
    M Eto
    Department of Cardiology, University Hospital, Institutes of Physiology, , Switzerland
    Circ Res 89:583-90. 2001
    ..These effects of thrombin may be important for endothelial dysfunction in cardiovascular disease, particularly during acute coronary episodes...

Research Grants66

  1. EGF Receptor Signaling in Time and Space in Tumor Cells
    Alexander D Sorkin; Fiscal Year: 2012
    ....
  2. Receptor-mediated actions of renin in kidney fibrosis
    Yufeng Huang; Fiscal Year: 2012
    ..That renin has bifunctional actions via different binding sites will be of enormous importance to be considered for new treatments targeting RAS in renal fibrosis. ..
  3. IFN AND ANTIPROLIFERATIVE SIGNALING PATHWAYS
    Andrew Larner; Fiscal Year: 2002
    ..3) Characterize and Purify Novel Proteins which may be required for IFN activation of B-Raf kinase. ..
  4. KININS ROLE IN MESANGIAL CELL FIBROSIS
    AYAD JAFFA; Fiscal Year: 2005
    ..abstract_text> ..
  5. ESTROGEN AND ENDOTHELIAL MIGRATION AND DIFFERENTIATION
    H Schnaper; Fiscal Year: 2002
    ..These studies will elucidate regulatory effects of estradiol on endothelial cell function. ..
  6. REGULATION OF C-MYB FUNCTION BY PHOSPHORYLATION
    TIMOTHY BENDER; Fiscal Year: 2000
    ..Next, proteins associated with c-myb will be isolated and identified. Finally, novel phosphorylation sites on c-myb will be identified and their putative roles in c-myb function will be determined. ..
  7. EFFECTS OF NITRIC OXIDE ON FETOPLACENTAL ANGIOGENESIS
    Jing Zheng; Fiscal Year: 2008
    ..An additional Specific Aim IV will use the HPME cell line to confirm the key observations made from OFPAE cells. These studies will glean important information on the mechanisms regulating placental angiogenesis. ..
  8. Pathogenesis of HIVAN: the role of Nef
    JOHN HE; Fiscal Year: 2007
    ..These studies should elucidate essential mechanism responsible for the development of HIV-associated nephropathy and how Nef plays a role in this pathologic process. ..
  9. Regulation of airway epithelial repair
    Steven R White; Fiscal Year: 2010
    ....
  10. CORTICOSTEROID INDUCED APOPTOSIS IN AIRWAY EPITHELIUM
    Steven White; Fiscal Year: 2002
    ..These data would help lead to new therapeutic ideas and modalities in the treatment of asthma to suppress inflammation while preventing mucosal damage. ..
  11. PKC Signaling in cAMP-Induced Pulmonary Vasodilation
    SCOTT BARMAN; Fiscal Year: 2010
    ..Progress of these studies will provide important knowledge towards the development of novel therapeutic agents that will help reduce the morbidity and mortality associated with pulmonary hypertension. ..
  12. PROTEIN SYNTHESIS INITIATION IN ANIMAL CELLS
    Bansidhar Datta; Fiscal Year: 2002
    ..This research is expected to provide valuable information regarding the mechanism of protein synthesis initiation in normal, cancerous, and virus- infected animal cells. ..
  13. Cyclic-AMP Induced Crypt Cell Survival in the Intestine
    Jeffrey Rudolph; Fiscal Year: 2008
    ....
  14. Intracellular signaling in anesthetic and hypoxic preconditioning of neurons
    Philip E Bickler; Fiscal Year: 2010
    ..The work will also identify why the aging brain may not be able to benefit from the neuroprotective actions of anesthetics or other preconditioning treatments. ..
  15. Renal medullary COX-2 in blood pressure control
    Tianxin Yang; Fiscal Year: 2008
    ..The information resulted from these studies will provide new insight into the molecular mechanism responsible for long-term control of arterial blood pressure. ..
  16. Ischemia-Reperfusion in A2A and A2B Knockout Hearts
    R Morrison; Fiscal Year: 2007
    ....
  17. Survival signaling in CNS neurons exposed to DNA damage
    Michal Hetman; Fiscal Year: 2008
    ..The proposed research may result in identification of new drug targets for treatment of neurological diseases and/or deleterious neurological side effects of cancer therapy. ..
  18. Mechanisms of Tumor Promotion Effects of B[a]PDE
    Chuanshu Huang; Fiscal Year: 2008
    ..Such agents could interfere with the signaling pathways leading to AP-1 activation. ..
  19. Cellular Signaling Mechanisms in Macrophage Activation.
    Joseph Cuschieri; Fiscal Year: 2007
    ..Through an enhanced understanding of these mechanisms it is our goal that potential therapeutic targets may be discovered to regulate the inflammatory response following trauma/hemorrhage and ischemia/reperfusion. ..
  20. The Role of Tuberin in Smooth Muscle Cell Proliferation
    Geraldine Finlay; Fiscal Year: 2007
    ..abstract_text> ..
  21. Cellular and Molecular Mechanisms of Vascular Permeability
    RADU STAN; Fiscal Year: 2009
    ..The techniques employed are cell fractionation, biochemical assays, cell free-assays, in-vivo transport studies, genetically modified animal models, cell culture, transfections, light and electron microscopy. ..
  22. Neuropilin-1 and VEGF-mediated pulmonary edema
    Patrice Becker; Fiscal Year: 2009
    ..Understanding basic mechanisms contributing to the development of pulmonary edema in ARDS may suggest novel therapeutic strategies for managing critically ill patients with this disorder. ..
  23. Structure and Function of Endothelial Fenestrae
    RADU VIRGIL STAN; Fiscal Year: 2010
    ..The techniques employed are cell isolation, fractionation, biochemical assays, cell free-assays, genetically modified animal models, cell culture, transfections, light and electron microscopy. ..
  24. Suppression of HIV-1 in CNS by a novel protein from ST John's Wort
    Shohreh Amini; Fiscal Year: 2010
    ..the future to devise therapeutic tools for halting viral gene expression and replication, and blocking Tat-induced stimulation of pro-inflammatory factors which are implicated in the pathogenesis of AIDS associated neurological problems ..
  25. Actions of Estrogen & Environmental Estrogens on Neurons
    Scott M Belcher; Fiscal Year: 2010
    ..The ability of ERa, ERp, and the orphan G-protein coupled receptor GPR30 to act as the membrane ER will be directly addressed. ..
  26. Growth Factors, Curcumin and Colon Carcinogenesis
    Pomila Singh; Fiscal Year: 2010
    ..The results of these studies are expected to help in developing mechanism-based strategies for preventative/treatment protocols for CRCusing curcumin like agents. ..
  27. MicroRNA-mediated Gene Regulation in Lung Development
    JINING LU; Fiscal Year: 2010
    ..Little is known how these molecules function in the embryonic lung and what genes they regulate. This study will provide insights into this issue and will help to understand mechanism of human diseases. ..
  28. Tat-mediated brain endothelial cell dysfunction
    Michal Toborek; Fiscal Year: 2009
    ..In a broader aspect, this proposal will contribute to better knowledge of how injury to brain endothelium can contribute to the development of neuroAIDS. ..
  29. Sphingosine-1-phosophate signaling in vasculogenesis
    KELLEY ARGRAVES; Fiscal Year: 2009
    ..Characterize the involvement of integrins in S1P-induced angioblast motility, and 3. Determine the significance S1P signaling to adult vasculogenesis mediated by circulating angioblasts. ..
  30. TYROSINE PHOSPHATASES IN ENDOTHELIAL GROWTH CONTROL
    Takamune Takahashi; Fiscal Year: 2009
    ..These complementary efforts will identify a novel pathway that regulates endothelial cell growth through CD148 and promise new strategies for anti-angiogenesis therapy. ..
  31. Cell cycle regulatory proteins in UVB-skin carcinogenes
    Arianna Kim; Fiscal Year: 2007
    ..In addition, our studies could provide a rationale to develop new therapeutic tools targeted towards the protein degradation machinery. ..
  32. BBB protection during treatment of transient ischemia
    Guo Yuan Yang; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  33. GLU6PASE AND 6P2K/FBASE GENE REGULATION IN SEPSIS
    SUBIR MAITRA; Fiscal Year: 2001
    ..The results of this study are essential to understand the molecular basis of deranged metabolism in sepsis. Understanding the mechanism might be useful for developing appropriate therapeutic intervention during sepsis. ..
  34. Bleomycin Hydrolase and Alzheimer's Disease
    JOHN LAZO; Fiscal Year: 2004
    ..These studies should provide new mechanistic information concerning the pathogenesis of AD as well as reagents for future therapeutic studies. ..
  35. Molecular & functional aspects of vascular permeability
    RADU STAN; Fiscal Year: 2004
    ..The techniques employed are cell fractionation, cell free-assays, in-vivo screening methods, two- dimensional electrophoresis, cell culture, transfections, light and electron microscopy. ..
  36. Transgenic Murine Model of Brain Vascular Malformation
    Guo Yuan Yang; Fiscal Year: 2004
    ..This non-tumor angiogenesis rodent preparation will serve as a model of disordered human cerebral angiogenesis, leading relatively quickly to the ability to test new therapeutic approaches for cerebrovascular disorders. ..
  37. MINIMAL ENTERAL NUTRIENT REQUIREMENTS IN NEONATES
    Douglas Burrin; Fiscal Year: 2004
    ....
  38. Actions of Estrogen & Environmental Estrogens on Neurons
    Scott Belcher; Fiscal Year: 2004
    ..From these results a neuronal "E2-signature cDNA array" will be developed and used in Aim 3 to determine how environmental estrogens influence E2-responsive gene expression in these developing neurons. ..
  39. Peptide Derivatives to treat Urinary Tract Infections
    Laszlo Otvos; Fiscal Year: 2003
    ..Our hope is that by the end of the grant period, we will be able to provide a pyrrhocoricin-derived peptide for ensuing US Food and Drug Administration-approved preclinical and clinical evaluation against urinary tract infections. ..
  40. VOLUME REGULATION IN CORNEAL ENDOTHELIUM
    SANGLY SRINIVAS; Fiscal Year: 2002
    ..abstract_text> ..
  41. PROTEIN KINASE C ISOTYPES IN LEUKEMIA CELL PHYSIOLOGY
    ALAN FIELDS; Fiscal Year: 2002
    ....
  42. 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. ..
  43. GENETIC APPROACH TO CNS REGENERATION RESEARCH
    Oswald Steward; Fiscal Year: 2001
    ....
  44. BIOCHEMICAL REGULATORS OF BLEOMYCIN INDUCED TUMORS
    JOHN LAZO; Fiscal Year: 2001
    ..The Specific Aims are to: 1) develop cells and mice deficient in BH, 2) develop cells and mice that overexpress BH, 3) isolate and characterize potential proteins that interact with BH and, 4) analyze the regulation of BH expression. ..
  45. POSTRECEPTOR DYSREGULATION IN DEPRESSION
    Yogesh Dwivedi; Fiscal Year: 2004
    ..abstract_text> ..
  46. Regulation and Function of MAPKAP Kinases
    Thomas Sturgill; Fiscal Year: 2005
    ..Aim four is to characterize the activation, enzymatic properties, and functions of MAPKAP kinase-like enzymes (Rcklp, Rck2p) in yeast, a model eukaryote, using combined biochemical and genetic approaches. ..
  47. Chemical Complementation Assay for MKP-1 (RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..This proposal will provide sufficient reagents, including cells and DMA transfection vectors, to permit the high throughput screening of 100,000 compounds. ..
  48. Interaction of COX-2 and nNOS in renin secretion
    Tianxin Yang; Fiscal Year: 2006
    ....
  49. Genistein and Asthma Pathogenesis
    Ravi Kalhan; Fiscal Year: 2006
    ..Exploring these mechanisms will expand the scientific rationale for tyrosine kinase inhibition as a therapeutic approach to asthmatic airway remodeling, and justify further study of the therapeutic role of soy isoflavones. ..
  50. Protein ubiquitination based neuroprotection for stroke
    Robert Meller; Fiscal Year: 2006
    ....
  51. Chemokines, nitric oxide, and myocardial depression
    Bysani Chandrasekar; Fiscal Year: 2005
    ..The results from these studies will further our knowledge of chemokine biology and lead to new therapeutic strategies to prevent or treat myocardial dysfunction in ischemia-reperfusion injury. ..
  52. Xenobiotics and Breast Epithelial Cell-ECM Signaling
    Raymond Novak; Fiscal Year: 2005
    ..The results of this proposal will provide novel information regarding chemical-mediated effects in breast epithelial cells and seminal data on fundamental cellular changes in human proliferative breast disease. ..
  53. In Vitro High Throughput Screening Assay for MKP-1(RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..No potent or selective small molecule inhibitors of this protein phosphatase are known. This proposal will provide sufficient reagents to permit a high throughput screening of 100,000 compounds. ..
  54. Protein Prenyltransferases in Glucose-Stimulated Insulin Secretion
    Anjaneyulu Kowluru; Fiscal Year: 2010
    ....
  55. Role of the Renin-Angiotensin System in the Regulation of Biliary Proliferation
    SHANNON STROUD GLASER; Fiscal Year: 2010
    ....
  56. IGFS & IGF-BINDING PROTEINS IN GROWTH & DIFFERENTIATION
    Pomila Singh; Fiscal Year: 2002
    ....
  57. AUTOCRINE ROLE OF GASTRIN-LIKE PEPTIDES IN COLON CANCER
    Pomila Singh; Fiscal Year: 2002
    ..If we are successful in purifying the novel GP-R (and confirm its role in mediating the mitogenic effects of gastrins) then one can develop systemic strategies to block the receptor mediated effects in future funding periods. ..
  58. Neuregulin-2 and the formation of neuromuscular synapses
    Mendell Rimer; Fiscal Year: 2006
    ..Results from the proposed research are expected to yield new insights into the molecular mechanisms that control neurotransmitter receptor density at the NMJ, which may bear on such control at synapses in the brain. ..
  59. 2003 Conference Pan-American Society Pigment Cell Resea
    Ruth Halaban; Fiscal Year: 2003
    ..3. To provide partial support to students and junior faculty to attend the meeting. They request funds for the 2003 meeting as well as for the 2 subsequent PASPCR annual meetings in years 2004 and 2006. ..
  60. Accelerated arthritis in E and P selectin deficient mice
    Jeffrey Ruth; Fiscal Year: 2007
    ..While common dogma suggests IL-1beta regulates selectins, this study proposes the novel hypothesis that in vivo E- and P-selectins regulate IL-1beta production and CIA development. [unreadable] [unreadable] [unreadable]..
  61. ROLE OF PROTEIN PHOSPHATASES IN INSULIN SECRETION
    Anjaneyulu Kowluru; Fiscal Year: 2004
    ....
  62. Nicotine/NNK Signaling in Human Lung Cancer Cells
    Xingming Deng; Fiscal Year: 2008
    ..abstract_text> ..
  63. Antigen-Specific CD8+ T Cell Responses by IL-21
    Protul Shrikant; Fiscal Year: 2008
    ..The insights provided by these investigations are likely to develop rational use of IL-21 alone or in combination with other cytokines for the therapy of cancer, infectious diseases, autoimmunity and transplantation. ..
  64. Commercialization of Embryonic Kidney Cell Lines
    Jeffrey Barnes; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..