mitogen activated protein kinase kinases

Summary

Summary: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.

Top Publications

  1. pmc BRAF mutation predicts sensitivity to MEK inhibition
    David B Solit
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nature 439:358-62. 2006
  2. 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
  3. pmc Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions
    W Kolch
    The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, U K
    Biochem J 351:289-305. 2000
  4. 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
  5. ncbi MAP kinases in the immune response
    Chen Dong
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98195 7650, USA
    Annu Rev Immunol 20:55-72. 2002
  6. ncbi Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta
    S Giroux
    Centre de recherche en cancérologie de l Université Laval, Centre Hospitalier Universitaire de Quebec, Pavillon L Hotel Dieu de Quebec, 9, a rue McMahon, Quebec, Canada, G1R 2J6
    Curr Biol 9:369-72. 1999
  7. ncbi Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38
    S J Harper
    Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Essex CM20 2QR, Harlow, UK
    Cell Signal 13:299-310. 2001
  8. ncbi Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes
    Abdelhamid Liacini
    Department of Medicine and Centre de Recherche du Centre Hospitalier de l Université de Montréal CHUM, Montreal, Quebec, Canada
    Exp Cell Res 288:208-17. 2003
  9. ncbi Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor
    N S Duesbery
    Advanced BioScience Laboratories Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Post Office Box B, Frederick, MD 21702
    Science 280:734-7. 1998
  10. ncbi The MAPK signaling cascade
    R Seger
    Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel
    FASEB J 9:726-35. 1995

Detail Information

Publications322 found, 100 shown here

  1. pmc BRAF mutation predicts sensitivity to MEK inhibition
    David B Solit
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nature 439:358-62. 2006
    ..These data suggest an exquisite dependency on MEK activity in BRAF mutant tumours, and offer a rational therapeutic strategy for this genetically defined tumour subtype...
  2. 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
    ....
  3. pmc Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions
    W Kolch
    The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, U K
    Biochem J 351:289-305. 2000
    ....
  4. 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...
  5. ncbi MAP kinases in the immune response
    Chen Dong
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98195 7650, USA
    Annu Rev Immunol 20:55-72. 2002
    ..In this review, we summarize recent progress in understanding the function and regulation of MAP kinase pathways in these phases of immune responses...
  6. ncbi Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta
    S Giroux
    Centre de recherche en cancérologie de l Université Laval, Centre Hospitalier Universitaire de Quebec, Pavillon L Hotel Dieu de Quebec, 9, a rue McMahon, Quebec, Canada, G1R 2J6
    Curr Biol 9:369-72. 1999
    ..They also suggest that mek1 function is required for normal response to angiogenic signals that might promote vascularization of the labyrinthine region of the placenta...
  7. ncbi Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38
    S J Harper
    Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Essex CM20 2QR, Harlow, UK
    Cell Signal 13:299-310. 2001
    ..We will examine the evidence that these pathways are important in neuronal cell death. Finally we will review the evidence that inhibitors of these pathways have a neuroprotective effect both in vitro and in vivo...
  8. ncbi Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes
    Abdelhamid Liacini
    Department of Medicine and Centre de Recherche du Centre Hospitalier de l Université de Montréal CHUM, Montreal, Quebec, Canada
    Exp Cell Res 288:208-17. 2003
    ..Blockade of TNF-alpha signaling and its target transcription factors by the approaches tested here may be beneficial for reducing cartilage breakdown by MMP-13 in arthritis...
  9. ncbi Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor
    N S Duesbery
    Advanced BioScience Laboratories Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Post Office Box B, Frederick, MD 21702
    Science 280:734-7. 1998
    ..The identification of a cleavage site for LF may facilitate the development of LF inhibitors...
  10. ncbi The MAPK signaling cascade
    R Seger
    Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel
    FASEB J 9:726-35. 1995
    ..In this review we emphasize primarily the first MAPK cascade to be discovered that uses the MEK and ERK isoforms and describe their involvement in different cellular processes...
  11. ncbi Integration of MAP kinase signal transduction pathways at the serum response element
    A J Whitmarsh
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605, USA
    Science 269:403-7. 1995
    ..The Elk-1 transcription factor therefore integrates MAP kinase signaling pathways in vivo to coordinate biological responses to different extracellular stimuli...
  12. ncbi Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages
    G Vitale
    Dipartimento di Scienze Biomediche, Universita di Padova, Italy
    Biochem Biophys Res Commun 248:706-11. 1998
    ..The possible implications of these findings for the cytolysis of macrophage cells induced by LF are discussed. These results open the way to the design and screening of specific inhibitors of LF...
  13. ncbi Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae
    K Y Choi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
    Cell 78:499-512. 1994
    ..Ste5 also increases the amount of Ste11 complexed to Ste7 and Fus3 and is required for Ste11 to function. These results substantiate a novel signal transduction component that physically links multiple kinases within a single cascade...
  14. ncbi Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase
    M P Scheid
    Jack Bell Research Centre, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada
    J Biol Chem 274:31108-13. 1999
    ..These results demonstrate for the first time in mammalian cells the involvement of the Ras-MAPK pathway in the phosphorylation of Bad and the regulation of its function...
  15. ncbi Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta
    Y Jiang
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 272:30122-8. 1997
    ..Nonetheless important differences exist among the four members of the p38 group of enzymes, and thus each may have highly specific, individual contributions to biologic events involving activation of the p38 pathways...
  16. ncbi Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway
    Jizhong Liu
    Institut National de la Sante et de la Recherche Medicale, Unité 837, Institut de Recherche sur le Cancer de Lille, France
    Blood 110:296-304. 2007
    ..Thus, B7-H1 expression by MM cells represents a possible immune escape mechanism that could be targeted therapeutically through inhibition of MyD88/TRAF6 and MEK/ERK/STAT1...
  17. pmc Expression of endogenous oncogenic V600EB-raf induces proliferation and developmental defects in mice and transformation of primary fibroblasts
    Kathryn Mercer
    Department of Biochemistry, University of Leicester, UK
    Cancer Res 65:11493-500. 2005
    ..Thus, (V600E)B-Raf is able to induce several hallmarks of transformation in some primary mouse cells without evidence for the involvement of a cooperating oncogene or tumor suppressor gene...
  18. pmc ERK activation promotes neuronal degeneration predominantly through plasma membrane damage and independently of caspase-3
    Srinivasa Subramaniam
    Neuroanatomy and Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 307, 2 OG, D 69120 Heidelberg, Germany
    J Cell Biol 165:357-69. 2004
    ..Antioxidants that reduced ERK activation and PM damage showed no effect on caspase-3 activation or DNA damage. These data identify ERK as an important executor of neuronal damage involving a caspase-3-independent mechanism...
  19. pmc A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates
    David T Ho
    Department of Developmental and Cell Biology, University of California, Irvine, California 92697, USA
    J Biol Chem 278:32662-72. 2003
    ..The MEK1 and MEK2 D-sites displayed a strong selectivity for their cognate MAPK (ERK2) versus a non-cognate MAPK (JNK). In contrast, the MKK4 D-site exhibited only limited selectivity for JNK versus ERK...
  20. ncbi G-protein-coupled receptors and signaling networks: emerging paradigms
    M J Marinissen
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research NIH, 30 Convent Drive, Building 30, Room 211, Bethesda, MD 20892 4340, USA
    Trends Pharmacol Sci 22:368-76. 2001
    ....
  21. ncbi Calcium-sensing receptor stimulates PTHrP release by pathways dependent on PKC, p38 MAPK, JNK, and ERK1/2 in H-500 cells
    J Tfelt-Hansen
    Endocrine Hypertension Division, Dept of Medicine and Membrane Biology Program, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA
    Am J Physiol Endocrinol Metab 285:E329-37. 2003
    ..We conclude that CaR regulation of PTHrP release in H-500 cells involves activation of PKC as well as the ERK1/2, p38 MAPK, and JNK pathways...
  22. ncbi Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2
    A Lin
    Department of Pharmacology, University of California San Diego School of Medicine, La Jolla 92093 0636, USA
    Science 268:286-90. 1995
    ..JNKK also activated another MAPK, p38 (Mpk2; the mammalian homolog of HOG1 from yeast), whose activity is regulated similarly to that of the JNKs...
  23. ncbi Regulation of epidermal growth factor-induced connexin 43 gap junction communication by big mitogen-activated protein kinase1/ERK5 but not ERK1/2 kinase activation
    Scott J Cameron
    Department of Pharmacology Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 278:18682-8. 2003
    ..These data indicate that BMK1 is more important than ERK1/2 in EGF-mediated Cx43 gap junction uncoupling by association and Cx43 Ser- 255 phosphorylation...
  24. ncbi CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK)
    Lee F Allen
    Department of Cancer Molecular Sciences, Ann Arbor, MI, USA
    Semin Oncol 30:105-16. 2003
    ....
  25. ncbi Phosphorylation of MEK1 by cdk5/p35 down-regulates the mitogen-activated protein kinase pathway
    Pushkar Sharma
    Laboratory of Neurochemistry, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:528-34. 2002
    ..Harada, T., Morooka, T., Ogawa, S., and Nishida, E. (2001) Nat. Cell Biol. 3, 453-459) have prompted us to propose a model for feedback down-regulation of the MAP kinase signal cascade by cdk5 inactivation of MEK1...
  26. ncbi Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4
    H Nishina
    The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, Suite 706, Toronto, Ontario M5G 2C1, Canada
    Development 126:505-16. 1999
    ..These results provide the first genetic link between stress-responsive kinases and organogenesis in mammals and indicate that SEK1 provides a crucial and specific survival signal for hepatocytes...
  27. pmc Signaling in the yeast pheromone response pathway: specific and high-affinity interaction of the mitogen-activated protein (MAP) kinases Kss1 and Fus3 with the upstream MAP kinase kinase Ste7
    L Bardwell
    Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, 94720 3202, USA
    Mol Cell Biol 16:3637-50. 1996
    ....
  28. pmc Activation of a mitogen-activated protein kinase pathway is involved in disease resistance in tobacco
    K Y Yang
    Department of Biochemistry, University of Missouri-Columbia, 117 Schweitzer Hall, Columbia, MO 65211, USA
    Proc Natl Acad Sci U S A 98:741-6. 2001
    ..These results demonstrate that a plant MAPK cascade controls multiple defense responses against pathogen invasion...
  29. pmc Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase
    A Salmeron
    Division of Cellular Immunology, National Institute of Medical Research, London, UK
    EMBO J 15:817-26. 1996
    ..Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1...
  30. ncbi Specificity of signaling from MAPKs to MAPKAPKs: kinases' tango nuevo
    Matthias Gaestel
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, D30625 Hannover, Germany
    Front Biosci 13:6050-9. 2008
    ..These mechanisms enable specific MAPK pathways to act independently via specific MAPKAPKs but also allow different MAPK pathways to cooperate in downstream signalling in a coordinated fashion...
  31. ncbi Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase
    J L Blank
    Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA
    J Biol Chem 271:5361-8. 1996
    ..These findings define a family of MEKK proteins capable of regulating sequential protein kinase pathways involving MAPK members...
  32. pmc Persistent activation by constitutive Ste7 promotes Kss1-mediated invasive growth but fails to support Fus3-dependent mating in yeast
    Seth Maleri
    Department of Biochemistry and Biophysics, CB 7260, 512 ME Jones, University of North Carolina, Chapel Hill, NC 27599 7260, USA
    Mol Cell Biol 24:9221-38. 2004
    ..This scaffold-independent activation of Kss1 by constitutive Ste7 and the existence of mechanisms for pathway-specific promoter discrimination impose a unique developmental fate independently of any distinguishing external stimuli...
  33. ncbi Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney
    T Yin
    Novartis Pharmaceuticals Corp, Summit, New Jersey 07901, USA
    J Biol Chem 272:19943-50. 1997
    ....
  34. pmc Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog
    K S Lee
    Department of Biochemistry, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205
    Mol Cell Biol 12:172-82. 1992
    ..This region may serve as a hinge between domains whose interaction is regulated by PKC1...
  35. ncbi Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6
    H Enslen
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605, USA
    J Biol Chem 273:1741-8. 1998
    ..The MKK3 and MKK6 signal transduction pathways are therefore coupled to distinct, but overlapping, groups of p38 MAP kinases...
  36. ncbi PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits
    P Ping
    Experimental Research Laboratory, Division of Cardiology, University of Louisville and Jewish Hospital Heart and Lung Institute, Louisville, Kentucky 40202, USA
    Am J Physiol 276:H1468-81. 1999
    ..The results are compatible with the hypothesis that p44 and p42 MAPKs may play a role in myocardial adaptations to ischemic stress...
  37. ncbi Activation of ERK1/2 MAP kinase pathway induces tight junction disruption in human corneal epithelial cells
    Yuan Wang
    Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912, USA
    Exp Eye Res 78:125-36. 2004
    ....
  38. pmc MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42
    G R Fanger
    Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO 80206, USA
    EMBO J 16:4961-72. 1997
    ..Differential MEKK subcellular distribution and interaction with small GTP-binding proteins provides a mechanism to regulate MAP kinase responses in localized regions of the cell and to different upstream stimuli...
  39. ncbi Cardiac hypertrophy induced by mitogen-activated protein kinase kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells
    Y Wang
    Department of Medicine, University of California at San Diego, La Jolla, California 92093, USA
    J Biol Chem 273:5423-6. 1998
    ..The cytopathic response, as a result of co-activation of both JNK and p38, may contribute to the loss of contractile function and viability of cardiomyocytes following hemodynamic overload and cardiac ischemia/reperfusion injury...
  40. ncbi Dynamic changes in the localization of MAPK cascade components controlling pathogenesis-related (PR) gene expression during innate immunity in parsley
    Justin Lee
    Department of Stress and Developmental Biology, Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle Saale, Germany
    J Biol Chem 279:22440-8. 2004
    ....
  41. pmc MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway
    J Raingeaud
    Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605 USA
    Mol Cell Biol 16:1247-55. 1996
    ..These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway...
  42. pmc Ubiquitin signalling in the NF-kappaB pathway
    Zhijian J Chen
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9148, USA
    Nat Cell Biol 7:758-65. 2005
    ..Recent studies have revealed several enzymes involved in the ubiquitination and deubiquitination of signalling proteins that mediate IKK activation through a degradation-independent mechanism...
  43. ncbi Rho GTPases and the control of cell behaviour
    A Hall
    MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, UK
    Biochem Soc Trans 33:891-5. 2005
    ..We have been analysing the biochemical contributions of Rho GTPases in cell movement and have found that Rac controls cell protrusion, while Cdc42 controls cell polarity...
  44. ncbi BCR-ABL mutants spread resistance to non-mutated cells through a paracrine mechanism
    J Liu
    INSERM, Unité 837, Equipe 3, Institut de Recherche sur le Cancer de Lille, Lille, France
    Leukemia 22:791-9. 2008
    ..Targeting JAK2 could eliminate both populations...
  45. ncbi Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expression
    Christian J Carlson
    Insulin Signaling, Metabolic Diseases Division, Global Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    Diabetes 52:634-41. 2003
    ..Furthermore, upregulation of the p38 pathway might contribute to the loss of GLUT4 expression observed in adipose tissue from type 2 diabetic patients...
  46. pmc Differential involvement of p38 mitogen-activated protein kinase kinases MKK3 and MKK6 in T-cell apoptosis
    Nobuyuki Tanaka
    Section of Immunobiology, Yale University School of Medicine, New Haven CT 06520, USA
    EMBO Rep 3:785-91. 2002
    ..In peripheral CD4(+)T cells, MKK3 is induced upon stimulation, whereas MKK6 is downregulated. These results suggest a novel mechanism regulating T-cell apoptosis differentially through the p38MAPK pathway by MKK3 and MKK6...
  47. ncbi Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells
    Ryo Fukuda
    McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Biol Chem 277:38205-11. 2002
    ..Involvement of the MAP kinase pathway represents a novel mechanism for the induction of HIF-1 alpha protein expression in human cancer cells...
  48. pmc ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents
    H van Dam
    Forschungszentrum Karlsruhe, Institut fur Genetik, Germany
    EMBO J 14:1798-811. 1995
    ..This allows fine tuned modulation of c-jun expression by a large spectrum of extracellular signals...
  49. ncbi The MAP kinase Fus3 associates with and phosphorylates the upstream signaling component Ste5
    J E Kranz
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
    Genes Dev 8:313-27. 1994
    ..These observations suggest the possibility that Ste5 promotes signal transduction by tethering Fus3 to its activating protein kinase(s)...
  50. pmc Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy
    R L Nicol
    Department of Molecular Biology, University of Texas, Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390 9148, USA
    EMBO J 20:2757-67. 2001
    ..These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly...
  51. pmc Multiple pathways differentially regulate global oxidative stress responses in fission yeast
    Dongrong Chen
    Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, United Kingdom
    Mol Biol Cell 19:308-17. 2008
    ..These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage...
  52. ncbi MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro
    B Errede
    Department of Chemistry, University of North Carolina, Chapel Hill 27599
    Nature 362:261-4. 1993
    ..Recent indications that MAP kinase activators are related to STE7 suggest that signal transduction pathways in many, if not all, eukaryotic organisms use homologous kinase cascades...
  53. pmc BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C
    Y Kato
    The Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    EMBO J 16:7054-66. 1997
    ..Taken together, these results strongly suggest that in some cell types the MEK5/BMK1 MAP kinase signaling pathway regulates serum-induced early gene expression through the transcription factor MEF2C...
  54. pmc Characterization of a serum response factor-like protein in Saccharomyces cerevisiae, Rlm1, which has transcriptional activity regulated by the Mpk1 (Slt2) mitogen-activated protein kinase pathway
    Y Watanabe
    Department of Molecular Biology, Faculty of Science, Nagoya University, Chikusa ku, Japan
    Mol Cell Biol 17:2615-23. 1997
    ....
  55. ncbi Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition
    Jin Mo Park
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0636, USA
    Science 297:2048-51. 2002
    ..This dismantling of the p38 MAPK module represents a strategy used by B. anthracis to paralyze host innate immunity...
  56. ncbi MEK, ERK, and p90RSK are present on mitotic tubulin in Swiss 3T3 cells: a role for the MAP kinase pathway in regulating mitotic exit
    F S Willard
    Molecular Signalling Group, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, GPO Box 334, A C T 2601, Canberra, Australia
    Cell Signal 13:653-64. 2001
    ..This failure to exit mitosis correlated with altered cyclin-dependent kinase (cdk) activities. Thus, the MAP kinase pathway may act to coordinate passage through mitosis in Swiss 3T3 fibroblasts by regulation of cdk activity...
  57. ncbi Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast
    J B Millar
    Division of Yeast Genetics, National Institute for Medical Research, Ridgeway, London, UK
    Genes Dev 9:2117-30. 1995
    ..We conclude that Pyp1 and Pyp2 are tyrosine-specific MAP kinase phosphatases that inactivate an osmoregulated MAP kinase, Sty1, which acts downstream of the Wis1 MAP kinase kinase to control cell size at division in fission yeast...
  58. pmc The JIP group of mitogen-activated protein kinase scaffold proteins
    J Yasuda
    Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Mol Cell Biol 19:7245-54. 1999
    ..The JIP proteins function by aggregating components of a MAP kinase module (including MLK, MKK7, and JNK) and facilitate signal transmission by the protein kinase cascade...
  59. ncbi Combinatorial control required for the specificity of yeast MAPK signaling
    H D Madhani
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 275:1314-7. 1997
    ..An FRE in the TEC1 promoter functions in a positive feedback loop required for pseudohyphal development...
  60. ncbi Interaction between two mitogen-activated protein kinases during tobacco defense signaling
    Yidong Liu
    Department of Biochemistry, University of Missouri Columbia, 117 Schweitzer Hall, 65211, USA
    Plant J 34:149-60. 2003
    ....
  61. pmc Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity
    D Yang
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605, USA
    Proc Natl Acad Sci U S A 94:3004-9. 1997
    ..These data establish that MKK4 is a JNK activator in vivo and demonstrate that MKK4 is an essential component of the JNK signal transduction pathway...
  62. ncbi Inhibition of the MAP kinase ERK protects from lipopolysaccharide-induced lung injury
    Katrin Schuh
    Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen Nuremberg, Erlangen, Germany
    Biochem Pharmacol 77:1827-34. 2009
    ..These data suggest that ERK signaling plays an important role in acute lung injury and pharmacologic inhibition of ERK provides a promising new therapeutic strategy for lung inflammatory diseases and in particular COPD...
  63. ncbi Manipulation of host signalling pathways by anthrax toxins
    Benjamin E Turk
    Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
    Biochem J 402:405-17. 2007
    ..Here I review recent progress in elucidating the mechanisms by which LF and EF influence host signalling and thereby contribute to disease...
  64. ncbi Coordinating ERK/MAPK signalling through scaffolds and inhibitors
    Walter Kolch
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
    Nat Rev Mol Cell Biol 6:827-37. 2005
    ..Computational modelling indicates that, together, these modulators can determine the dynamic biological behaviour of the pathway...
  65. ncbi ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity
    Ru Rong Ji
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
    J Neurosci 22:478-85. 2002
    ..Activation of the ERK pathway in a subset of nociceptive spinal neurons contributes, therefore, to persistent pain hypersensitivity, possibly via transcriptional regulation of genes, such as prodynorphin and NK-1...
  66. 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
    ....
  67. ncbi Ancient signals: comparative genomics of plant MAPK and MAPKK gene families
    Louis Philippe Hamel
    Natural Resources Canada, Canadian Forest Service, Laurentian Forestry Centre, 1055 du PEPS, Sainte Foy, Quebec, Canada G1V 4C7
    Trends Plant Sci 11:192-8. 2006
    ..The Arabidopsis MAPK nomenclature appears sufficiently robust to allow it to be usefully extended to other well-characterized plant systems...
  68. pmc Mitogen-activated protein kinase kinase activity is required for the G(2)/M transition of the cell cycle in mammalian fibroblasts
    J H Wright
    Department of Pharmacology, University of Washington, Seattle, WA 98103, USA
    Proc Natl Acad Sci U S A 96:11335-40. 1999
    ..These data demonstrate a novel role for the MAPK cascade in progression from G(2) into mitosis in NIH 3T3 cells...
  69. pmc Tyrosine-phosphorylated extracellular signal--regulated kinase associates with the Golgi complex during G2/M phase of the cell cycle: evidence for regulation of Golgi structure
    H Cha
    Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, Maryland 21201, USA
    J Cell Biol 153:1355-67. 2001
    ..These data provide the first evidence that pY ERK and not ERK kinase activity regulates Golgi structure and may be involved in mitotic Golgi fragmentation and reformation...
  70. ncbi A novel tobacco mitogen-activated protein (MAP) kinase kinase, NtMEK1, activates the cell cycle-regulated p43Ntf6 MAP kinase
    O Calderini
    Institute of Microbiology and Genetics, University of Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria
    J Biol Chem 276:18139-45. 2001
    ..Expression analysis showed that the NtMEK1 and ntf6 genes are co-expressed both in plant tissues and following the induction of cell division in leaf pieces. These data suggest that NtMEK1 is an MEK for the p43(Ntf6) MAP kinase...
  71. ncbi The MEK1-ERK map kinase pathway and the PI 3-kinase-Akt pathway independently mediate anti-apoptotic signals in HepG2 liver cancer cells
    H Mitsui
    First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
    Int J Cancer 92:55-62. 2001
    ..These data indicate that survival of HepG2 liver cancer cells depends upon serum and that both the MEK1-ERK- and the PI 3-kinase-Akt- pathways are required for survival signaling to the nucleus...
  72. ncbi Mechanistic studies of the dual phosphorylation of mitogen-activated protein kinase
    J E Ferrell
    Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305 5332, USA
    J Biol Chem 272:19008-16. 1997
    ....
  73. ncbi Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative
    H Ellinger-Ziegelbauer
    Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1876, USA
    J Biol Chem 272:2668-74. 1997
    ..The ability of MEKK3 to simultaneously activate the SAPK and ERK pathways is remarkable, given that they have divergent roles in cellular homeostasis...
  74. pmc A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function
    A D Catling
    Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville 22908, USA
    Mol Cell Biol 15:5214-25. 1995
    ..These observations indicate a critical role for the PR sequence in directing specific protein-protein interactions important for the activation, inactivation, and downstream functioning of the MEKs...
  75. ncbi JNK is required for effector T-cell function but not for T-cell activation
    C Dong
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 405:91-4. 2000
    ..However, production of effector T-cell cytokines did require JNK. Thus, JNK is necessary for T-cell differentiation but not for naive T-cell activation...
  76. ncbi Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms
    B Derijard
    Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605
    Science 267:682-5. 1995
    ..These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways...
  77. ncbi Characterization of two cDNAs that encode MAP kinase homologues in Arabidopsis thaliana and analysis of the possible role of auxin in activating such kinase activities in cultured cells
    T Mizoguchi
    Laboratory of Plant Molecular Biology, Institute of Physical and Chemical Research RIKEN, Tsukuba Life Science Center, Tsukuba, Ibaraki, Japan
    Plant J 5:111-22. 1994
    ..These results suggest that auxin may function as an activator of plant MAP kinase homologues, as do various mitogens in animal systems...
  78. pmc A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras
    M Kretzschmar
    Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021 USA
    Genes Dev 13:804-16. 1999
    ..Our results suggest a mechanism for the counterbalanced regulation of Smad2/Smad3 by TGFbeta and Ras signals in normal cells, and for the silencing of antimitogenic TGFbeta functions by hyperactive Ras in cancer cells...
  79. ncbi The Arabidopsis thaliana MEK AtMKK6 activates the MAP kinase AtMPK13
    Balázs Melikant
    Max F Perutz Laboratories, University Departments at the Vienna Biocenter, Institute of Microbiology and Genetics, University of Vienna, Dr Bohr Gasse 9, A 1030 Vienna, Austria
    FEBS Lett 576:5-8. 2004
    ..RT-PCR analysis showed the co-expression of these two genes in diverse plant tissues. These data show that AtMKK6 can functionally activate the MAP kinase AtMPK13...
  80. ncbi Differential roles of ERK and p38 MAP kinase pathways in positive and negative selection of T lymphocytes
    T Sugawara
    Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan
    Immunity 9:565-74. 1998
    ..These results suggest that intracellular signals through different MAP kinase cascades selectively guide positive and negative selection of T lymphocytes...
  81. ncbi The ERK cascade as a prototype of MAPK signaling pathways
    Hadara Rubinfeld
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Methods Mol Biol 250:1-28. 2004
  82. ncbi Mitogen-activated protein kinase kinase 2 activation is essential for progression through the G2/M checkpoint arrest in cells exposed to ionizing radiation
    D W Abbott
    Vanderbilt University Departments of Cell Biology and Pathology and the Vanderbilt University Cancer Center, Nashville, Tennessee 37232, USA
    J Biol Chem 274:2732-42. 1999
    ....
  83. ncbi Constitutively active mitogen-activated protein kinase kinase 1 (MAPKK1) and MAPKK2 mediate similar transcriptional and morphological responses
    S J Mansour
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309, USA
    Cell Growth Differ 7:243-50. 1996
    ..Altogether, the results demonstrate that the two isoforms elicit similar responses in vivo despite differences in their regulation...
  84. pmc Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes
    H Nishina
    Amgen Institute and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Ontario, Canada
    J Exp Med 186:941-53. 1997
    ..Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL-2 production and T cell proliferation...
  85. pmc Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells
    Joao T Barata
    Tumor Biology Unit, Institute of Molecular Medicine, University of Lisbon Medical School, 1649 028, Lisbon, Portugal
    J Exp Med 200:659-69. 2004
    ....
  86. ncbi MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion
    P B Mehta
    Prostate Research Group, Department of Surgery, The Medical School, University of Newcastle upon Tyne, Framlington Place, UK
    Oncogene 22:1381-9. 2003
    ..Taken together, our results establish MEK5 as a key signalling molecule associated with prostate carcinogenesis. As the MEK5/ERK5 interaction is highly specific, it represents a potential target of therapy...
  87. pmc Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process
    Laurence Abrami
    Department of Genetics and Microbiology, University of Geneva, 1211 Geneva 4, Switzerland
    J Cell Biol 160:321-8. 2003
    ..e., slow endocytosis as a monomer and rapid clathrin-mediated uptake on clustering, make it an ideal anthrax toxin receptor...
  88. ncbi Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3
    H Nishina
    The Amgen Institute, Ontario Cancer Institute, Toronto, Canada
    Nature 385:350-3. 1997
    ..These data indicate that SEK1 mediates survival signals in T-cell development...
  89. ncbi Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun
    I Sanchez
    Diabetes Research Laboratory, Massachusetts General Hospital East, Charlestown
    Nature 372:794-8. 1994
    ..Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor...
  90. pmc Relative dependence of different outputs of the Saccharomyces cerevisiae pheromone response pathway on the MAP kinase Fus3p
    F W Farley
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genetics 151:1425-44. 1999
    ..Finally, suppression analysis argues that Kss1p contributes to the overall pheromone response in a wild-type strain, but that Fus3p is the critical kinase for all of the outputs tested...
  91. ncbi MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous
    P M Holland
    Fred Hutchinson Cancer Research Center, A2 025, Seattle, Washington 98109, USA
    J Biol Chem 272:24994-8. 1997
    ..MKK7 directly phosphorylates and activates JNK/SAPK. Thus, MKK7 is a homolog of hep and functions in a conserved signaling pathway involving JNK/SAPK and the GTPase Rac1...
  92. pmc Mek2 is dispensable for mouse growth and development
    Louis François Bélanger
    Centre de recherche en cancérologie de l Université Laval, Centre Hospitalier Universitaire de Quebec, Quebec, Quebec, Canada G1R 2J6
    Mol Cell Biol 23:4778-87. 2003
    ..Altogether, our findings demonstrate that MEK2 is not necessary for the normal development of the embryo and T-cell lineages, suggesting that the loss of MEK2 can be compensated for by MEK1...
  93. ncbi The p38 pathway provides negative feedback for Ras proliferative signaling
    G Chen
    Cleveland Clinic Foundation, Department of Molecular Biology, Cleveland, Ohio 44195, USA
    J Biol Chem 275:38973-80. 2000
    ..These studies thus establish a negative feedback mechanism by which Ras proliferative activity is regulated via signaling integrations of MAPK pathways...
  94. pmc NQK1/NtMEK1 is a MAPKK that acts in the NPK1 MAPKKK-mediated MAPK cascade and is required for plant cytokinesis
    Takashi Soyano
    Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa ku, Japan
    Genes Dev 17:1055-67. 2003
    ..Thus, NQK1/NtMEK1 (ANQ1) MAPKK appears to be a positive regulator of plant cytokinesis during meiosis as well as mitosis...
  95. ncbi Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast
    K Shiozaki
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Genes Dev 10:2276-88. 1996
    ..However, unlike spc1- mutants, atf1- cells have no mitotic cell-cycle defect, indicating that the stress response pathway bifurcates at Spc1 to regulate independently meiosis and mitosis...
  96. pmc Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway
    Laurence Abrami
    Department of Microbiology and Molecular Medicine, University of Geneva, 1 rue Michel Servet, Geneva, Switzerland 1211
    J Cell Biol 166:645-51. 2004
    ....
  97. ncbi Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis
    U Acharya
    Department of Biology, University of California, San Diego, La Jolla 92093 0347, USA
    Cell 92:183-92. 1998
    ..However, the known cytoplasmic substrates for MEK1, ERK1, and ERK2 are not required for this process. Interestingly, we find a Golgi-associated ERK, which we propose as the likely target for MEK1 in Golgi fragmentation...
  98. ncbi The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast
    M G Wilkinson
    Division of Yeast Genetics, National Institute for Medical Research, London, UK
    Genes Dev 10:2289-301. 1996
    ..These findings highlight a remarkable level of conservation in transcriptional control by stress-activated MAP kinase pathways between fission yeast and mammalian cells...
  99. pmc Mitogen-activated protein kinases and nuclear factor-kappaB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages
    Asima Bhattacharyya
    Department of Chemistry, Bose Institute, 93 1 Acharya Prafulla Chandra Road, Kolkata 700009, India
    Biochem J 368:121-9. 2002
    ..pylori amplifies the inflammatory response associated with gastric H. pylori infection and needs to be taken into consideration when developing therapeutics based on these signalling pathways...
  100. ncbi RAS/RAF pathway activation in gliomas: the result of copy number gains rather than activating mutations
    Judith Jeuken
    Department of Pathology, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500, Nijmegen, The Netherlands
    Acta Neuropathol 114:121-33. 2007
    ..These results indicate that RAS/RAF pathway activation in gliomas is achieved much more frequently by copy number gains including RAS/RAF and/or upstream growth factor (receptor) than by activating RAS/RAF mutations...
  101. ncbi Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade
    S Pleschka
    , , , D-35392 Giessen, Germany
    Nat Cell Biol 3:301-5. 2001
    ..Thus, signalling through the mitogenic cascade seems to be essential for virus production and RNP export from the nucleus during the viral life cycle...

Research Grants63

  1. Genetic variation and regulatory networks: Mechanisms and complexity
    DANA PE ER; Fiscal Year: 2009
    ..These tools will be made publicly available, including a friendly graphical user interface and visualization. ..
  2. Development of an effective therapy against post-exposure Anthrax
    Maurizio Pellecchia; Fiscal Year: 2010
    ..Such inhibitors will be tested as single agents and in combination with antibiotics, in order to develop the most efficacious post-exposure therapy that should facilitate and assure the recovery of patients who harbor the disease. ..
  3. Heat Shock-Induced Apoptosis
    Shawn B Bratton; Fiscal Year: 2012
    ..Thus, it is anticipated that the work proposed herein will significantly improve our understanding of how heat shock works in the clinic and may shed light on new pathways that can be exploited therapeutically in the future. ..
  4. Inhibition of Anthrax Lethal Factor by alpha-defensins
    Wuyuan Lu; Fiscal Year: 2011
    ..abstract_text> ..
  5. Novel Mekk1-p53 mediated transcriptional regulation: mechanism and genome wide st
    M Rafiq Islam; Fiscal Year: 2010
    ....
  6. Signaling Mechanisms in Plant Innate Immunity
    Jen Sheen; Fiscal Year: 2012
    ....
  7. Characterization of Anthrax Lethal Toxin
    JEREMY S MOGRIDGE; Fiscal Year: 2010
    ..Lethal factor is the enzymatic component of the toxin that cleaves mitogen activated protein kinase kinases after being delivered to the mammalian cell cytosol by the second toxin component, protective ..
  8. Identification of novel mammalian genes required for intoxication by antrax toxin
    G Jilani Chaudry; Fiscal Year: 2012
    ..LF is a Zn-dependent metalloprotease that cleaves mitogen activated protein kinase kinases (MAPKKs)...
  9. Alcohol Injury Healing, Cytoprotection and Survivin
    Michael Jones; Fiscal Year: 2009
    ..Information gained from these studies will lead to better understanding of the mechanisms underlying ETOH-induced injury and will provide for the development of better therapeutics for treating ETOH-induced injury. ..
  10. Mechanisms of ER Stress and Neurodegeneration in Parkinson's Disease
    Eric J Huang; Fiscal Year: 2013
    ..Our results will bring further insights to the mechanisms of ER stress in PD, and provide novel therapeutic targets for the treatment of this devastating disease. ..
  11. Coordinated regulation of MAP kinase signaling by ubiquitination
    JILLIAN HEYWARD HURST; Fiscal Year: 2012
    ..This proposal aims to identify a new mechanism that regulates cellular signaling and possibly reveal new ways to modulate signaling pathways to combat disease. ..
  12. Signaling Cascades in Regulation of Pancreatic Beta cell mass.
    Ulupi S Jhala; Fiscal Year: 2012
    ..2) Examine downstream molecular mechanisms by which mixed lineage kinases regulate beta cell death. 3) Examination of post-translational mechanisms that regulate the activation of MLKs in the pancreatic beta cell. ..
  13. Human Choriogonadotropin Signaling in Cell Proliferation
    MICHAEL HUDECKI; Fiscal Year: 2003
    ..abstract_text> ..
  14. Development of Therapeutic Inhibitors to Anthrax Toxins
    JOHNNY PETERSON; Fiscal Year: 2006
    ..anthracis, increase the efficacy of antibiotics, promote killing of the bacteria by phagocytes, and enhance vaccine-induced immunity. [unreadable] [unreadable]..
  15. ROLES OF PKC ISOFORMS IN COLONIC CARCINOGENESIS
    Marc Bissonnette; Fiscal Year: 2002
    ....
  16. LINKING OF PROTEIN TYROSINE AND SERINE PHOSPHORYLATION
    EDWIN KREBS; Fiscal Year: 1999
    ..This research is relevant to neoplastic disease and also to metabolic hormonal disorders such as diabetes mellitus. ..
  17. LPS SIGNAL TRANSDUCTION IN NEUTROPHILS
    JERRY NICK; Fiscal Year: 2001
    ..The comprehensive study of this signal transduction pathway may lead to new approaches for modifying LPS induced inflammatory responses. (End of abstract) ..
  18. Effects of tumor lethal factor on Kaposi's Sarcoma
    NICHOLAS DUESBERY; Fiscal Year: 2005
    ..Several years ago I established that LeTx proteolytically inactivates mitogen activated protein kinase kinases (MAPKKs or MEKs)...
  19. CHARACTERIZATION OF A NOVEL MAP/ERK KINASE
    Marsha Rosner; Fiscal Year: 2004
    ..abstract_text> ..
  20. Mechanisms of Growth Factor-Estrogen Receptor Crosstalk
    Stephen Safe; Fiscal Year: 2006
    ..abstract_text> ..
  21. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    Aminah Ikner; Fiscal Year: 2004
    ..It is expected that knowledge obtained in yeast is very informative to understand the regulation of human MAPK cascades, which play crucial roles in cellular proliferation and physiology. ..
  22. The Impact of Anthrax Toxin on Embryonic Development
    JIMMY BALLARD; Fiscal Year: 2004
    ..We will determine the impact inactive anthrax toxin mutants have on zebrafish embryo development. Specific aim 2 will address the possibility that vaccine and therapeutic candidates might cause developmental defects. ..
  23. INSULIN-REGULATED MAP KINASE PATHWAYS
    Melanie Cobb; Fiscal Year: 2006
    ..We will examine the mechanisms of ERK5 regulation, and determine how its actions relate to the functions of ERK1/2. We will also study a putative ERK5 ortholog in C. elegans to use genetic studies to complement work in mammals. ..
  24. STRUCTURAL ORGANIZATION OF SIGNALING PATHWAYS
    Roger Davis; Fiscal Year: 2004
    ..The Specific Aims of this proposal are to examine: 1. The physiological role of JIP scaffold proteins. 2. The structure and dynamics of JIP scaffold complexes. 3. The mechanism of JIP-stimulated JNK activity. ..
  25. ERK Signaling in Food-Restricted, Drug-Sensitive Rats
    Sandra Haberny; Fiscal Year: 2004
    ..The third aim is to determine, by measuring photobeam interruption to count movements, whether PD98059 reverses the augmented SKF-82958-induced locomotor activity that is otherwise observed in FR compared to AL rats. ..
  26. Host Factors Influencing Anthrax Toxin Sensitivity
    Ana Sanchez; Fiscal Year: 2005
    ..Additionally, we will conduct somatic cell and chemical genetic screens using a toxin sensitive macrophage cell line to identify cellular factors or processes that play a role LF sensitivity. ..
  27. OSMOREGULATORY SIGNAL TRANSDUCTION IN YEAST
    Haruo Saito; Fiscal Year: 2002
    ..Finally, the SHO1 osmosensing mechanism will be genetically analyzed. ..
  28. 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. ..
  29. 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. ..
  30. Lung Cancer Chemoprevention using Deguelin
    Ho Young Lee; Fiscal Year: 2008
    ..abstract_text> ..
  31. Mechanisms of K+ Channel Modulation in Plasticity
    Laura Schrader; Fiscal Year: 2007
    ..In addition, we will study their modulation in hippocampal neurons, assayed by biochemical and immunohistochemical techniques. ..
  32. MATERNAL ALCOHOLISM AND CNS DEVELOPMENT IN OFFSPRING
    MARY DRUSE MANTEUFFEL; Fiscal Year: 2007
    ..Analyses will include western blot analyses, real-time quantitative RT-PCR, fluorescence and light microscopy, immunohistochemistry, and enzyme assays. ..
  33. Regulation of Oocyte Viability by Granulosa Cell Contact
    John Peluso; Fiscal Year: 2004
    ..abstract_text> ..
  34. 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. ..
  35. Progesterone regulation of human luteal cell viability
    John Peluso; Fiscal Year: 2006
    ..Such selective manipulation of the P4's actions could have far reaching effects on the treatment for infertility, contraception and certain types of cancers. [unreadable] [unreadable]..
  36. Host defense functions of M. tuberculosis lipoglycan
    Edward Chan; Fiscal Year: 2005
    ..3. To elucidate the role of the TLRs, MAPK and NFkB signaling pathways, and ManLAM in controlling the growth of M. tuberculosis in mouse and human macrophages and to correlate effects on growth with NO* and TNFa expression. ..
  37. Poly (ADP-Ribose) synthetase in expression of endothelia
    Basilia Zingarelli; Fiscal Year: 2003
    ..abstract_text> ..
  38. Protein Kinase G Regulation of Granulosa Cell Viability
    John Peluso; Fiscal Year: 2006
    ..We now propose to test this hypothesis using biochemical, genetic, imaging and cell biological techniques. [unreadable] [unreadable]..
  39. ROLE OF PKD IN LEUKOCYTE ACTIVATION BY CPG DNA
    Ae Kyung Yi; Fiscal Year: 2002
    ..This proposed study would enhance our understanding of how CpG motifs in bacterial DNA break immune tolerance and contribute to chrome inflammatory autoimmune diseases such as arthritis. ..
  40. Induction of immunological paralysis by CpG DNA
    Ae Kyung Yi; Fiscal Year: 2008
    ..abstract_text> ..
  41. Biomarkers of COX-2 inhibitors in intraductal papillary mucinous neoplasm (IPMN)
    Christian Schmidt; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  42. MEK singaling in sarcoma growth and vascularization.
    NICHOLAS DUESBERY; Fiscal Year: 2007
    ..i ..
  43. Correlative trial of fenretinide against Glioblastomas
    VINAY PUDUVALLI; Fiscal Year: 2003
    ..Such data could be relevant not only to future trials of retinoids in gliomas but also for ongoing trials of fenretinide in other malignancies. ..
  44. Radiation injury to the heart
    John E Baker; Fiscal Year: 2010
    ..1 ..
  45. CREB and Synaptic Reorganization
    Karl Obrietan; Fiscal Year: 2007
    ..An understanding of the intracellular signaling events that couple seizures to synaptic remodeling should allow for the development of therapeutic approaches designed to block the development of some forms of epilepsy. ..
  46. Control of T Lymphopoiesis and Growth by Mad Genes
    Brian Iritani; Fiscal Year: 2007
    ..abstract_text> ..
  47. MECHANISMS OF DIETARY MODULATION OF MELANOMA INVASION
    GARY MEADOWS; Fiscal Year: 2003
    ..abstract_text> ..
  48. REGULATION OF MITOSIS IN FISSION YEAST
    Paul Russell; Fiscal Year: 2003
    ..The aim of these experiments will be to understand how activation of nuclear Cdc2/cyclin-B is coordinated with signals that indicate cell size and cell physiology that are presumed to emanate from cytoplasm. ..
  49. Development of ERK docking domain inhibitors
    Paul Shapiro; Fiscal Year: 2005
    ..These studies represent a novel approach for developing compounds that selectively block ERK activation of proteins involved in cancer cell proliferation. ..
  50. Oxidant induced gene expression in vitamin E deficient *
    Kishorchandra Gohil; Fiscal Year: 2002
    ..These molecular data may provide the basis for designing more effective protocols for dietary interventions with antioxidants that might ameliorate lung diseases induced by environmental oxidants. ..
  51. SQUAMOUS EPITHELIAL CELL INVASION IN ORGAN CULTURE
    James Varani; Fiscal Year: 2001
    ..abstract_text> ..
  52. NEURAL MECHANISMS OF ADAPTIVE BEHAVIOR
    Joyce Keifer; Fiscal Year: 2009
    ..For research focused on the changes to neural function induced by chronic social stress during adolescence, and to direct pharmacotherapy of associated psychiatric disorders. ..
  53. IKKBeta Mediated Impairment of Endothelial Nitric Oxide Production
    Francis Kim; Fiscal Year: 2010
    ..Aim 3. To determine whether the Toll Like Receptor pathway is necessary for endothelial activation of IKKbeta during the development of vascular insulin resistance. ..
  54. Mechanisms of NF-kappaB Activation in T Lymphocytes
    Zhijian Chen; Fiscal Year: 2008
    ..Such knowledge is crucial to understanding and treating various human diseases, including MALT lymphoma and other immune disorders. ..
  55. Anti-inflammatory Natural Product Mode of Action Studies
    CRAIG CREWS; Fiscal Year: 2008
    ..abstract_text> ..
  56. Prognostic Markers for Juvenile Pilocytic Astrocytomas
    Kwong Kwok Wong; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  57. Effects of HAART drugs on endothelial dysfunction of pu*
    Changyi Chen; Fiscal Year: 2009
    ..abstract_text> ..
  58. UCLA SPORE IN LUNG CANCER
    Steven Dubinett; Fiscal Year: 2008
    ..The UCLA Lung Cancer SPORE constitutes a highly collaborative, multi-disciplinary translational research program designed to make a significant impact on lung cancer. ..
  59. ALCOHOL AND THE CONTROL OF LIVER REGENERATION
    JOANNES HOEK; Fiscal Year: 2008
    ..We expect that a better understanding of these early signaling events may lead to the development of rational therapies for ethanol-induced liver damage [unreadable] [unreadable]..
  60. Role of JAM Family in Angiogenesis
    Ulhas P Naik; Fiscal Year: 2010
    ..Further, elucidation of the role of JAM-A in endothelial cell proliferation and migration leading to angiogenesis will open up a mew line of investigation that is important in tumerigenesis and vascular biology. ..
  61. EARLY RESPONSE OF CORNEAL EPITHELIUM TO UV-INDUCED DEATH
    Luo Lu; Fiscal Year: 2004
    ..Furthermore therapeutic measures may be identified which could reduce the incidence of UV-induced apoptotic corneal epithelial damage and increases in corneal epithelial susceptibility to infection and diseases. ..
  62. LRRK2 and cellular pathways of Parkinson's Disease
    Wanli Smith; Fiscal Year: 2007
    ....
  63. MAP Kinase and AKT Signaling in Congestive Heart Failure
    ANTHONY MUSLIN; Fiscal Year: 2009
    ..Our findings will help to identify specific signaling mechanisms involved in the regulation of cardiac myocyte growth and metabolism. ..