p38 mitogen activated protein kinases

Summary

Summary: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.

Top Publications

  1. ncbi Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation
    J M Kyriakis
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
    Physiol Rev 81:807-69. 2001
  2. ncbi p38 MAP-kinases pathway regulation, function and role in human diseases
    Ana Cuenda
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochim Biophys Acta 1773:1358-75. 2007
  3. ncbi LPS induction of gene expression in human monocytes
    M Guha
    Departments of Immunology, C-204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Signal 13:85-94. 2001
  4. ncbi Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases
    Gary L Johnson
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Science 298:1911-2. 2002
  5. ncbi A protein kinase involved in the regulation of inflammatory cytokine biosynthesis
    J C Lee
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406
    Nature 372:739-46. 1994
  6. ncbi Activation and signaling of the p38 MAP kinase pathway
    Tyler Zarubin
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Res 15:11-8. 2005
  7. pmc p38(MAPK): stress responses from molecular mechanisms to therapeutics
    Lydia R Coulthard
    NIHR Leeds Musculoskeletal Biomedical Research Unit, St James s University Hospital, Leeds, LS9 7TF, UK
    Trends Mol Med 15:369-79. 2009
  8. ncbi Inhibition of p38 MAP kinase as a therapeutic strategy
    J C Lee
    SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA
    Immunopharmacology 47:185-201. 2000
  9. pmc ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions
    Philippe P Roux
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Microbiol Mol Biol Rev 68:320-44. 2004
  10. ncbi p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia
    Ru Rong Ji
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
    Neuron 36:57-68. 2002

Detail Information

Publications418 found, 100 shown here

  1. ncbi Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation
    J M Kyriakis
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
    Physiol Rev 81:807-69. 2001
    ..The nuclear factor-kappa B pathway, a second stress signaling paradigm, has been the subject of several excellent recent reviews (258, 260)...
  2. ncbi p38 MAP-kinases pathway regulation, function and role in human diseases
    Ana Cuenda
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochim Biophys Acta 1773:1358-75. 2007
    ..Here we focus on these emergent roles of p38MAPKs and their implication in different pathologies...
  3. ncbi LPS induction of gene expression in human monocytes
    M Guha
    Departments of Immunology, C-204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Signal 13:85-94. 2001
    ..These signaling pathways in turn activate a variety of transcription factors that include NF-kappaB (p50/p65) and AP-1 (c-Fos/c-Jun), which coordinate the induction of many genes encoding inflammatory mediators...
  4. ncbi Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases
    Gary L Johnson
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Science 298:1911-2. 2002
    ..The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity...
  5. ncbi A protein kinase involved in the regulation of inflammatory cytokine biosynthesis
    J C Lee
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406
    Nature 372:739-46. 1994
    ..Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production...
  6. ncbi Activation and signaling of the p38 MAP kinase pathway
    Tyler Zarubin
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Res 15:11-8. 2005
    ..Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38...
  7. pmc p38(MAPK): stress responses from molecular mechanisms to therapeutics
    Lydia R Coulthard
    NIHR Leeds Musculoskeletal Biomedical Research Unit, St James s University Hospital, Leeds, LS9 7TF, UK
    Trends Mol Med 15:369-79. 2009
    ..Furthermore, we discuss how the p38(MAPK) pathway might be best exploited for the development of more effective therapeutics with minimal side effects in a range of specific disease settings...
  8. ncbi Inhibition of p38 MAP kinase as a therapeutic strategy
    J C Lee
    SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA
    Immunopharmacology 47:185-201. 2000
    ..Treatment with p38 MAP kinase inhibitors attenuated both p38 activation and disease severity. Structurally diverse p38 MAP kinase inhibitors have been tested extensively in preclinical studies...
  9. pmc ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions
    Philippe P Roux
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Microbiol Mol Biol Rev 68:320-44. 2004
    ..In this article, we review the existing data on the MKs and discuss their physiological functions based on recent discoveries...
  10. ncbi p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia
    Ru Rong Ji
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
    Neuron 36:57-68. 2002
    ....
  11. ncbi Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation
    J Han
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nature 386:296-9. 1997
    ..One consequence of MEF2C activation is increased c-jun gene transcription. Our results show that p38 may influence host defence and inflammation by maintaining the balance of c-Jun protein consumed during infection...
  12. ncbi Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway
    Dmitry V Bulavin
    Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 36:343-50. 2004
    ..We conclude that inactivation or depletion of the Wip1 phosphatase with resultant p38 MAPK activation suppresses tumor appearance by modulating the Cdkn2a tumor-suppressor locus...
  13. ncbi Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development
    Katsunori Nakata
    Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California 95064, USA
    Cell 120:407-20. 2005
    ..DLK-1 protein levels are elevated in rpm-1 mutants. The RPM-1 RING finger can stimulate ubiquitination of DLK-1. Our data reveal a presynaptic role of a previously unknown p38 MAP kinase cascade...
  14. 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
    ....
  15. ncbi Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interf
    S J Ajizian
    Crippled Children s Foundation Research Center at Le Bonheur Children sMedical Center, Memphis, TN 38103, USA
    J Infect Dis 179:939-44. 1999
    ....
  16. ncbi A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells
    J Han
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037
    Science 265:808-11. 1994
    ..Both HOG1 and p38 are tyrosine phosphorylated after extracellular changes in osmolarity. These findings link a signaling pathway in mammalian cells with a pathway in yeast that is responsive to physiological stress...
  17. ncbi Mitogen-activated protein kinases in apoptosis regulation
    Teiji Wada
    IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohr gasse3 5, Vienna A 1030, Austria
    Oncogene 23:2838-49. 2004
    ..In this review, we discuss MAPKs in apoptosis regulation with attention to mouse genetic models and critically point out the multiple roles of MAPKs...
  18. ncbi Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing
    Camilla I Svensson
    Department of Anesthesiology, University of California, San Diego, La Jolla, California, USA
    J Neurochem 86:1534-44. 2003
    ..Taken together, these results indicate that spinal p38 MAPK is involved in inflammation-induced pain and that activated spinal microglia play a direct role in spinal nociceptive processing...
  19. ncbi p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment
    Simona Saccani
    Institute for Research in Biomedicine, Via Vela 6, CH 6501, Bellinzona, Switzerland
    Nat Immunol 3:69-75. 2002
    ..These results show that p38 plays an additional role in the induction of the inflammatory and immune response: the regulation of NF-kappa B recruitment to selected chromatin targets...
  20. ncbi p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci
    Cristiano Simone
    Laboratory of Gene Expression, Dulbecco Telethon Institute at Fondazione A Cesalpino, Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park of Rome, Rome 00128, Italy
    Nat Genet 36:738-43. 2004
    ..These results identify an unexpected function of differentiation-activated p38 in converting external cues into chromatin modifications at discrete loci, by selectively targeting SWI-SNF to muscle-regulatory elements...
  21. ncbi Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase
    X Z Wang
    Department of Medicine, Skirball Institute of Biomolecular Medicine, New York University Medical Center, 10016, NY, USA
    Science 272:1347-9. 1996
    ..CHOP thus serves as a link between a specific stress-activated protein kinase, p38, and cellular growth and differentiation...
  22. pmc p38 and extracellular signal-regulated kinases regulate the myogenic program at multiple steps
    Z Wu
    Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093 0322, USA
    Mol Cell Biol 20:3951-64. 2000
    ..Importantly, activation of ERK is inhibitory toward myogenic transcription in myoblasts but contributes to the activation of myogenic transcription and regulates postmitotic responses (i.e., hypertrophic growth) in myotubes...
  23. ncbi MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation
    Isaac A Manke
    Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Mol Cell 17:37-48. 2005
    ..We propose that MAPKAP kinase-2 is a new member of the DNA damage checkpoint kinase family that functions in parallel with Chk1 and Chk2 to integrate DNA damage signaling responses and cell cycle arrest in mammalian cells...
  24. ncbi p38 mitogen-activated protein kinase is required for TGFbeta-mediated fibroblastic transdifferentiation and cell migration
    Andrei V Bakin
    Department of Medicine, Vanderbilt University School of Medicine, 777 Preston Research Building, Nashville, TN 37232, USA
    J Cell Sci 115:3193-206. 2002
    ..These studies suggest that the p38MAPK pathway is required for TGFbeta-mediated EMT and cell migration...
  25. ncbi Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease
    Eike Hollenbach
    Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany
    FASEB J 18:1550-2. 2004
    ..Thus, RICK could represent a novel target for future therapies in human IBD...
  26. ncbi MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis
    A Kotlyarov
    Martin Luther University Halle Wittenberg, Germany
    Nat Cell Biol 1:94-7. 1999
    ..We conclude that MK2 is an essential component in the inflammatory response which regulates biosynthesis of TNF-alpha at a post-transcriptional level...
  27. ncbi p38 MAP kinases: beyond the stress response
    A R Nebreda
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Trends Biochem Sci 25:257-60. 2000
  28. pmc Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses
    Hongbo Chi
    Section of Immunobiology, Department of Pharmacology, and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 103:2274-9. 2006
    ..These results highlight the complex mechanisms by which the MAPKs regulate innate immunity...
  29. pmc MAP kinase and pain
    Ru Rong Ji
    Pain Research Center, Department of Anesthesiology, Brigham and Women s Hospital and Harvard Medical School, 75 Francis Street, MRB 604, Boston, MA 02115, USA
    Brain Res Rev 60:135-48. 2009
    ..Although it is well documented that MAPK pathways can increase pain sensitivity via peripheral mechanisms, this review will focus on central mechanisms of MAPKs, especially ERK...
  30. pmc Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor alpha mRNA stability
    K R Mahtani
    Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, Hammersmith, London W6 8LH, United Kingdom
    Mol Cell Biol 21:6461-9. 2001
    ..Our findings demonstrate a direct link between a specific signal transduction pathway and a specific RNA-binding protein, both of which are known to regulate TNF-alpha gene expression at a posttranscriptional level...
  31. ncbi Angiogenesis in collagen I requires alpha2beta1 ligation of a GFP*GER sequence and possibly p38 MAPK activation and focal adhesion disassembly
    Shawn M Sweeney
    Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 278:30516-24. 2003
    ..Thus capillary morphogenesis requires endothelial alpha2beta1 integrin engagement of a single type I collagen integrin-binding site, possibly signaling via p38 MAPK and focal adhesion disassembly/FAK inactivation...
  32. ncbi Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase
    D V Bulavin
    Division of Basic Science, National Cancer Intitute, National Institutes of Health, Bethesda, MD 20892, USA
    Nature 411:102-7. 2001
    ..We propose that regulation of Cdc25B phosphorylation by p38 is a critical event for initiating the G2/M checkpoint after ultraviolet radiation...
  33. 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...
  34. pmc p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage
    H Christian Reinhardt
    Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18 580, Cambridge, MA 02139, USA
    Cancer Cell 11:175-89. 2007
    ..We show that the Chk1 inhibitor UCN-01 also potently inhibits MK2, suggesting that its clinical efficacy results from the simultaneous disruption of two critical checkpoint pathways in p53-defective cells...
  35. ncbi MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits
    Bozena Kaminska
    Department of Cell Biology, Laboratory of Transcription Regulation, Nencki Institute of Experimental Biology, 3 Pasteur Str, 02 093 Warsaw, Poland
    Biochim Biophys Acta 1754:253-62. 2005
    ..Moreover, many of these drugs are small molecules that can be administered orally, and initial results of clinical trials have shown clinical benefits in patients with chronic inflammatory disease...
  36. ncbi Pharmacological effects of SB 220025, a selective inhibitor of P38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models
    J R Jackson
    Department of Immunopharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Pharmacol Exp Ther 284:687-92. 1998
    ..Thus, this p38/CSBP MAP kinase inhibitor, which can reduce inflammatory cytokine production and inhibit angiogenesis, is an effective treatment for chronic proliferative inflammatory disease...
  37. pmc Mechanism of p38 MAP kinase activation in vivo
    Deborah Brancho
    Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Genes Dev 17:1969-78. 2003
    ..These data indicate that p38 MAPK is regulated by the coordinated and selective actions of three different protein kinases in response to cytokines and exposure to environmental stress...
  38. pmc The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor
    R Beyaert
    Laboratory of Molecular Biology, University of Ghent, Belgium
    EMBO J 15:1914-23. 1996
    ..Interestingly, TNF-induced cytotoxicity was not affected by SB203580, indicating that p38 MAP kinase might be an interesting target to interfere selectively with TNF-induced gene activation...
  39. pmc Distinct cellular functions of MK2
    Alexey Kotlyarov
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    Mol Cell Biol 22:4827-35. 2002
    ..These data indicate that catalytic activity of MK2 is required for both cytokine production and cell migration. However, the proline-rich MK2 N terminus provides a distinct role restricted to cell migration...
  40. ncbi Regulation of cyclooxgenase-2 mRNA stability by taxanes: evidence for involvement of p38, MAPKAPK-2, and HuR
    Kotha Subbaramaiah
    Department of Medicine Division of Gastroenterology and Hepatology, New York Presbyterian Hospital, New York, New York 10021, USA
    J Biol Chem 278:37637-47. 2003
    ..To the best of our knowledge, this is the first evidence that taxanes can promote stabilization of mRNA in addition to modulating gene transcription...
  41. ncbi Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
    Keisuke Ito
    Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano machi, Shinjuku ku, Tokyo 160 8582, Japan
    Nat Med 12:446-51. 2006
    ..These data show that inactivation of p38 MAPK protects HSCs against loss of self-renewal capacity. Our characterization of molecular mechanisms that limit HSC lifespan may lead to beneficial therapies for human disease...
  42. ncbi Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes
    Abdelhamid Liacini
    Département de Médecine and Centre de Recherche du Centre Hospitalier de l Université de Montréal, Hôpital Notre Dame du CHUM, 1560 Sherbrooke Est, Montreal, Quebec, Canada H2L 4M1
    Matrix Biol 21:251-62. 2002
    ..Inhibition of IL-1 signal transduction by these agents could be useful for reducing cartilage resorption by MMPs in arthritis...
  43. ncbi Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is independent of p53
    S S Bacus
    Quantitative Diagnostic Laboratories, Inc, Elmhurst, Illinois 60126, USA
    Oncogene 20:147-55. 2001
    ..However, p53 may serve as a survival factor in breast carcinoma cells treated with Taxol by blocking cells in G2/M phase of the cell cycle...
  44. ncbi ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity
    Atsushi Matsuzawa
    Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Nat Immunol 6:587-92. 2005
    ..Our data demonstrate that the reactive oxygen species-dependent TRAF6-ASK1-p38 axis is crucial for TLR4-mediated mammalian innate immunity...
  45. pmc Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation
    D V Bulavin
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 18:6845-54. 1999
    ..These results suggest that p38 kinase plays a prominent role in an integrated regulation of N-terminal phosphorylation that regulates p53-mediated apoptosis after UV radiation...
  46. pmc TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses
    Li Yu
    Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    EMBO J 21:3749-59. 2002
    ..These results indicate that TGF-beta receptor signals through multiple intracellular pathways and provide first-hand biochemical evidence for the existence of Smad-independent TGF-beta receptor signaling...
  47. pmc Epithelial cells are sensitive detectors of bacterial pore-forming toxins
    Adam J Ratner
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 281:12994-8. 2006
    ..Osmosensing may thus represent a novel innate immune response to a common bacterial virulence strategy...
  48. ncbi A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity
    Dennis H Kim
    Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
    Science 297:623-6. 2002
    ..These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species...
  49. pmc Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2
    A J Waskiewicz
    Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    EMBO J 16:1909-20. 1997
    ..MNK1 may define a convergence point between the growth factor-activated and one of the stress-activated protein kinase cascades and is a candidate to phosphorylate eIF-4E in cells...
  50. ncbi Signal pathway of hypoxia-inducible factor-1alpha phosphorylation and its interaction with von Hippel-Lindau tumor suppressor protein during ischemia in MiaPaCa-2 pancreatic cancer cells
    Seok J Kwon
    Department of Surgery, School of Medicine, University of Pittsburgh, PA 15213, USA
    Clin Cancer Res 11:7607-13. 2005
    ..Human pancreatic cancer MiaPaCa-2 cells were exposed to low glucose (0.1 mmol/L) with hypoxia (0.1% O(2))...
  51. ncbi p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix
    Xueying Wang
    The Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Republic of Singapore
    Endocrinology 148:1629-37. 2007
    ..These findings identify a novel mechanism by which p38 MAPK regulates osteoblast differentiation...
  52. ncbi Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms
    Kai Soo Tan
    The Comprehensive Center for Inflammatory Disorders, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599, USA
    Cell Signal 19:251-60. 2007
    ....
  53. doi Change in histone H3 phosphorylation, MAP kinase p38, SIR 2 and p53 expression by resveratrol in preventing streptozotocin induced type I diabetic nephropathy
    Kulbhushan Tikoo
    Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research NIPER, Punjab, India
    Free Radic Res 42:397-404. 2008
    ..This is the first report which suggests that protection against development of diabetic nephropathy by resveratrol treatment involves change in phosphorylation of histone H3, expression of Sir-2, p53 and p38 in diabetic kidney...
  54. ncbi Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells
    Z Guan
    Department of Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 273:28670-6. 1998
    ..This study suggests that the activation of both JNK/SAPK and p38 MAPK signaling cascades is required for IL-1beta-induced Cox-2 expression and PGE2 synthesis...
  55. ncbi Mitogen-activated protein kinase phosphatase-1 is a mediator of breast cancer chemoresistance
    George W Small
    The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Cancer Res 67:4459-66. 2007
    ....
  56. pmc Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins
    Danielle L Huffman
    Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, 92093, USA
    Proc Natl Acad Sci U S A 101:10995-1000. 2004
    ..Our data demonstrate that cells defend against pore-forming toxins by means of conserved MAPK pathways...
  57. ncbi Nerve conduction blockade in the sciatic nerve prevents but does not reverse the activation of p38 mitogen-activated protein kinase in spinal microglia in the rat spared nerve injury model
    Yeong Ray Wen
    Pain Research Center, Department of Anesthesiology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Anesthesiology 107:312-21. 2007
    ..Nerve injury-induced ectopic spontaneous activity is essential for the generation of neuropathic pain. The authors examined whether peripheral neural activity is necessary for p38 activation in spinal microglia...
  58. ncbi Src phosphorylates Tyr284 in TGF-beta type II receptor and regulates TGF-beta stimulation of p38 MAPK during breast cancer cell proliferation and invasion
    Amy J Galliher
    Department of Pharmacology, University of Colorado Health Sciences Center, 12801 East 17th Avenue, Aurora, CO 80045, USA
    Cancer Res 67:3752-8. 2007
    ....
  59. ncbi Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis--CREB and NF-kappaB as key regulators
    Jin Mo Park
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA
    Immunity 23:319-29. 2005
    ..Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival...
  60. ncbi Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense
    A W Roberts
    Howard Hughes Medical Institute, and Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202, USA
    Immunity 10:183-96. 1999
    ..Rac2 is an essential regulator of multiple specialized neutrophil functions...
  61. 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...
  62. ncbi Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system
    Mark Pickering
    Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Exp Physiol 90:663-70. 2005
    ..In the following review we look at these and other effects of TNF-alpha in the CNS...
  63. ncbi MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer
    L Xu
    Department of Medicine, Division of Hematology Oncology, Northwestern University Medical School, Chicago, IL, USA
    Oncogene 25:2987-98. 2006
    ..This study demonstrates that both MAPKAPK2 and HSP27 are necessary for TGFbeta-mediated increases in MMP-2 and cell invasion in human prostate cancer...
  64. ncbi The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascades
    Katsushi Yamamoto
    Department of Molecular Embryology, Chiba University Graduate School of Medicine, 1 8 1 Inohana, Chuo Ku, Chiba 260 8670, Japan
    J Biol Chem 278:34525-32. 2003
    ..These results indicate that the KDEL receptor participates in the ER stress response not only by its retrieval ability but also by modulating MAP kinase signaling, which may affect the outcomes of the mammalian ER stress response...
  65. ncbi TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells
    Eun Sook Kim
    College of Pharmacy, Duksung Women s University, Seoul 132 714, Korea
    Int J Oncol 25:1375-82. 2004
    ....
  66. ncbi Mechanical stress-induced DNA damage and rac-p38MAPK signal pathways mediate p53-dependent apoptosis in vascular smooth muscle cells
    Manuel Mayr
    Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria
    FASEB J 16:1423-5. 2002
    ..The latter lost their ability to express Bax and showed no apoptosis in response to cyclic strain. Taken together, our data provide the first evidence that SMC apoptosis induced by mechanical stress is p53-dependent...
  67. ncbi Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability
    Patrice M Becker
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Circ Res 96:1257-65. 2005
    ..These data support a critical role for Npn-1 in regulating endothelial barrier dysfunction in response to VEGF and suggest that activation of distinct receptor complexes may determine specificity of cellular response to VEGF...
  68. pmc Smad-dependent GADD45beta expression mediates delayed activation of p38 MAP kinase by TGF-beta
    Mutsuhiro Takekawa
    Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4 6 1, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    EMBO J 21:6473-82. 2002
    ..Thus TGF-beta-induced p38 activation, mediated by GADD45beta expression, may play an important role in the biological effects of TGF-beta...
  69. ncbi p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils
    M J Rane
    Department of Medicine, University of Louisville Health Sciences Center and the Veterans Affairs Medical Center, Louisville, Kentucky 40202, USA
    J Biol Chem 276:3517-23. 2001
    ..We conclude that Akt exists in a signaling complex containing p38 kinase, MK2, and Hsp27 and that p38-dependent MK2 activation functions as PDK2 in human neutrophils...
  70. ncbi Evidence of STAT1 phosphorylation modulated by MAPKs, MEK1 and MSK1
    Yiguo Zhang
    Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
    Carcinogenesis 25:1165-75. 2004
    ..Overall, our data indicate that phosphorylation of STAT1 at Ser727 occurs through diverse MAPK cascades including MEK1, ERKs, p38 kinase, JNKs and MSK1 in the cellular response to UVA...
  71. ncbi Hyperosmolality causes growth arrest of murine kidney cells. Induction of GADD45 and GADD153 by osmosensing via stress-activated protein kinase 2
    D Kultz
    Laboratory of Kidney and Electrolyte Metabolism, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1603, USA
    J Biol Chem 273:13645-51. 1998
    ....
  72. ncbi p38 MAP kinase: a convergence point in cancer therapy
    James M Olson
    Fred Hutchinson Cancer Research Center, and Department of Pediatrics, University of Washington, Seattle, WA, USA
    Trends Mol Med 10:125-9. 2004
    ..Here, we review p38-MAPK-mediated tumor cell apoptosis and implications for cancer therapeutics...
  73. ncbi The involvement of p38 mitogen-activated protein kinase in the alpha-melanocyte stimulating hormone (alpha-MSH)-induced melanogenic and anti-proliferative effects in B16 murine melanoma cells
    K Smalley
    Department of Oncology, University College London, 91 Riding House Street, W1P 8BT, London, UK
    FEBS Lett 476:198-202. 2000
    ..It therefore appears that activation of the p38 pathway can promote melanogenesis and inhibit growth of B16 melanoma cells...
  74. ncbi Aplidin induces apoptosis in human cancer cells via glutathione depletion and sustained activation of the epidermal growth factor receptor, Src, JNK, and p38 MAPK
    Ana Cuadrado
    Drug Discovery Department, PharmaMar S A, Tres Cantos, E 28760 Madrid, Spain
    J Biol Chem 278:241-50. 2003
    ..These data provide a molecular basis for the anticancer activity of Aplidin...
  75. ncbi Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages
    Peili Chen
    Stress Signaling Unit, Laboratory of Cellular and Molecular Biology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
    J Immunol 169:6408-16. 2002
    ..These findings highlight MKP-1 as a critical negative regulator of the macrophage inflammatory response, underscoring its premise as a potential target for developing novel anti-inflammatory drugs...
  76. ncbi MAPK pathways in radiation responses
    Paul Dent
    Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298 0058, USA
    Oncogene 22:5885-96. 2003
    ..This review will describe the enzymes within the known MAPK signaling pathways and discuss their activation and roles in cellular radiation responses...
  77. ncbi Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket
    R J Gum
    Department of Molecular Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 273:15605-10. 1998
    ..These results indicate that these three amino acids can confer specificity and sensitivity to SB 203580 for at least two different classes of MAPKs...
  78. ncbi Stabilization of IFN-gamma mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells
    Athanasios Mavropoulos
    Kennedy Institute of Rheumatology Division, Imperial College London, London, United Kingdom
    Blood 105:282-8. 2005
    ..Therefore, the synergistic induction of IFN-gamma by IL-12 and IL-18 in natural killer cells is mediated at least in part by p38-dependent and 3' UTR-mediated stabilization of IFN-gamma mRNA...
  79. 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...
  80. 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...
  81. ncbi p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Mayer 557, 44 Binney Street, Boston, MA 02115, USA
    Oncogene 23:8766-76. 2004
    ..These studies therefore provide the framework for clinical trials of SCIO-469 to enhance sensitivity and overcome resistance to PS-341, thereby improving patient outcome in MM...
  82. pmc The role of ATF-2 family transcription factors in adipocyte differentiation: antiobesity effects of p38 inhibitors
    Toshio Maekawa
    RIKEN Tsukuba Institute, 3 1 1 Koyadai, Tsukuba, Ibaraki 305 0074, Japan
    Mol Cell Biol 30:613-25. 2010
    ..In p38 inhibitor-treated mice, macrophage infiltration into WAT was reduced and the tumor necrosis factor alpha (TNF-alpha) levels were lower than control mice. Thus, p38 inhibitors may provide a novel antiobesity treatment...
  83. ncbi Endoplasmic reticulum stress stimulates the expression of cyclooxygenase-2 through activation of NF-kappaB and pp38 mitogen-activated protein kinase
    Jui Hsiang Hung
    Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China
    J Biol Chem 279:46384-92. 2004
    ..Our results provide important insights into cellular carcinogenesis associated with latent endoplasmic reticulum stress...
  84. ncbi Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade
    P Juo
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 8:1001-8. 1998
    ..The intracellular domain of Fas interacts with several proteins including FADD (MORT-1), DAXX, RIP, FAF-1, FAP-1 and Sentrin. The adaptor protein FADD can, in turn, interact with the cysteine protease caspase-8 (FLICE/MACH/Mch5)...
  85. doi p38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta
    Rama Kamesh Bikkavilli
    Department of Pharmacology, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY 11794 8651, USA
    J Cell Sci 121:3598-607. 2008
    ..We demonstrate the involvement of G-proteins and Dishevelleds in Wnt3a-induced p38 MAPK activation, highlighting a critical role for p38 MAPK in canonical Wnt-beta-catenin signaling...
  86. ncbi p38 MAP kinase mediates inflammatory cytokine induction in cardiomyocytes and extracellular matrix remodeling in heart
    Manxiang Li
    Department of Physiology, University of Maryland, School of Medicine, Baltimore, USA
    Circulation 111:2494-502. 2005
    ..Yet, the myocyte contribution to their induction in failing hearts and the underlying regulatory mechanism in stressed myocardium remain unclear...
  87. ncbi Intrathecal minocycline attenuates peripheral inflammation-induced hyperalgesia by inhibiting p38 MAPK in spinal microglia
    Xiao Ying Hua
    Department of Anaesthesiology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0818, USA
    Eur J Neurosci 22:2431-40. 2005
    ....
  88. ncbi Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies
    D Kontoyiannis
    Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece
    Immunity 10:387-98. 1999
    ..e., chronic inflammatory arthritis and Crohn's-like inflammatory bowel disease, suggests that defective function of ARE may be etiopathogenic for the development of analogous human pathologies...
  89. pmc Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation
    Tina M Thornton
    Department of Medicine Immunobiology Program, University of Vermont, Burlington, VT 05405 0068, USA
    Science 320:667-70. 2008
    ..Activation of beta-catenin-mediated signaling through GSK3beta inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues...
  90. ncbi Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia
    F C Barone
    SmithKline Beecham Pharmaceuticals, Department of Cardiovascular Pharmacology, King of Prussia, PA 19406, USA
    Med Res Rev 21:129-45. 2001
    ....
  91. pmc The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK
    N Ronkina
    Institute of Biochemistry, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Mol Cell Biol 27:170-81. 2007
    ..This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels...
  92. ncbi Angiotensin-(1-7) inhibits angiotensin II-stimulated phosphorylation of MAP kinases in proximal tubular cells
    Z Su
    Division of Nephrology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China
    Kidney Int 69:2212-8. 2006
    ..Generation of Ang-(1-7) by proximal tubular ACE2 could thereby serve a protective role by counteracting the effects of locally generated Ang II...
  93. ncbi Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide-stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages
    M Caivano
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, United Kingdom
    J Immunol 164:3018-25. 2000
    ..They also suggest that MSK1 and MSK2 may play a role in these processes and hence are potential targets for the development of novel antiinflammatory drugs...
  94. ncbi C-reactive protein inhibits chemotactic peptide-induced p38 mitogen-activated protein kinase activity and human neutrophil movement
    R M Heuertz
    Department of Internal Medicine, Saint Louis University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 274:17968-74. 1999
    ..7144). These data show that signal transduction through p38 MAP kinase is necessary for neutrophil chemotaxis and that CRP intercedes through this pathway in inhibiting neutrophil movement...
  95. ncbi Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 AND p38 mitogen-activated protein kinase pathways
    K Subbaramaiah
    Department of Medicine, New York Presbyterian Hospital Cornell and Strang Cancer Prevention Center, New York, New York 10021, USA
    J Biol Chem 275:14838-45. 2000
    ..Thus, microtubule- or actin-interfering agents stimulated MAPK signaling and activator protein-1 activity. This led, in turn, to induction of COX-2 gene expression via the cyclic AMP response element site in the COX-2 promoter...
  96. ncbi Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha
    Xiaochun Jin
    Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 26:246-55. 2006
    ..These results suggest that TNFalpha may induce acute peripheral mechanical sensitization by acting directly on TNFR1 in primary afferent neurons, resulting in p38-dependent modulation of TTX-resistant Na+ channels...
  97. ncbi Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site
    Christopher Pargellis
    Department of Biology, Boehringer Ingelheim Pharmaceuticals, Research and Development Center, 900 Ridgebury Road, Ridgefield, Connecticut 06877, USA
    Nat Struct Biol 9:268-72. 2002
    ..One of the most potent compounds in this series, BIRB 796, has picomolar affinity for the kinase and low nanomolar inhibitory activity in cell culture...
  98. pmc E47 phosphorylation by p38 MAPK promotes MyoD/E47 association and muscle-specific gene transcription
    Frederic Lluis
    Center for Genomic Regulation, Program on Differentiation and Cancer, Barcelona, Spain
    EMBO J 24:974-84. 2005
    ..These findings identify a novel pro-myogenic role of p38 in regulating the formation of functional MyoD/E47 heterodimers that are essential for myogenesis...
  99. ncbi Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well a
    Qinwen Wang
    Department of Physiology and Pharmacology, Trinity College, Dublin 2, Ireland
    J Neurosci 24:3370-8. 2004
    ..These studies provide evidence that the Abeta-mediated inhibition of LTP induction involves stimulation of the kinases JNK, Cdk5, and p38 MAPK after the activation of both the Abeta receptor(s) and mGluR5...
  100. doi Tumor necrosis factor receptor 1 induces interleukin-6 upregulation through NF-kappaB in a rat neuropathic pain model
    Kyung Min Lee
    Department of Anatomy, School of Medicine, Kyungpook National University, 2 101, Dongin Dong, Daegu 700 422, South Korea
    Eur J Pain 13:794-806. 2009
    ....
  101. doi The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
    Alessandro Sorrentino
    Ludwig Institute for Cancer Research, Rudbeck Laboratory, Uppsala University, Sweden, Dag Hammarskjoldsv 20, SE 75185 Uppsala, Sweden
    Nat Cell Biol 10:1199-207. 2008
    ..Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6...

Research Grants69

  1. Chymase-Mediated MMP Activation in Ishemia Reperfusion Injury
    LOUIS JOSEPH DELL'ITALIA; Fiscal Year: 2013
    ....
  2. Antiphospholipid antibodies and lupus: new molecular targets for treatment
    Emilio B Gonzalez; Fiscal Year: 2013
    ..These studies may help to devise new more specific and less harmful modalities than the anticoagulation or general immunosuppression currently used to treat and prevent thrombosis in patients with aPL Abs. ..
  3. P38 MAP KINASE SIGNALING IN SKIN
    Tatiana Efimova; Fiscal Year: 2013
    ..We are optimistic that the completion of the proposed studies will result in a better mechanistic understanding of the p384 role in epithelial carcinogenesis and its potential as an anti-cancer therapeutic target. ..
  4. Neuroprotection by IFN-beta in AIDS
    Marcus Kaul; Fiscal Year: 2013
    ....
  5. The Postischemia Inflammatory Syndrome in the Aged Kidney
    KATHERINE JULIA KELLY; Fiscal Year: 2013
    ..Nearly one-half of patient beginning dialysis for CKD were e65 yo. We propose to study inflammatory and vascular injury and cell death and the effects of potential therapies in a model of CKD. ..
  6. Anthrax Toxins Impair Phagocyte Actin-based Motility
    Frederick Southwick; Fiscal Year: 2010
    ....
  7. Regulation of Bile Acid Synthesis by Nuclear Receptors in Vivo
    Gregorio Gil; Fiscal Year: 2012
    ..The successful completion of this study will provide us with new insights into the molecular mechanisms involved in the regulation of bile acid biosynthesis. ..
  8. Retinoid Mediated Protection Against Reactive Oxygen Species Induced Cytotoxicity
    Serrine S Lau; Fiscal Year: 2013
    ....
  9. Targeting Tight Junctions To Treat Mucositis
    FREDERICK GARY TOBACK; Fiscal Year: 2010
    ..This project is aimed at learning how this protein fragment exerts its biological effects because when it is given to mice or hamsters with experimental oral mucositis, it protects against and speeds recovery from injury. ..
  10. Estrogen receptor, p38 MAPKs and topo IIa in breast cancer
    Guan Chen; Fiscal Year: 2013
    ..Since breast cancer is a major malignant disease for female veterans, this study will contribute significantly to veteran's health care. ..
  11. MOLECULAR MODELS OF IMMUNE-MEDIATED VASCULAR INJURY
    Jeffrey R Bender; Fiscal Year: 2012
    ....
  12. CHONDROPROTECTIVE ACTIVITY OF POMEGRANATE EXTRACT
    Tariq M Haqqi; Fiscal Year: 2010
    ..Our findings are likely to open the door for the development of novel therapeutic strategies for the treatment of OA. ..
  13. Mechanisms that Regulate Neonatal Lung Heme Oxygenase in Hyperoxia
    Phyllis A Dennery; Fiscal Year: 2013
    ....
  14. Beta-adrenergic regulation of adipose tissue function by PKA and MAP kinases
    Sheila Collins; Fiscal Year: 2009
    ..PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page ..
  15. Histone Deacetylation Regulates Growth Plate Development
    Lei Wei; Fiscal Year: 2013
    ..The understanding of cell differentiation in growth plate may also be important to the understanding of abnormal chondrocyte differentiation in osteoarthritis. ..
  16. Targeting Injury Pathways to Counteract Pulmonary Agent and Vesicant Toxicity
    Sven Eric Jordt; Fiscal Year: 2013
    ..We identified a new group of drugs that we found to effectively diminish injury by chlorine gas and skin blistering agents. The goal of this proposal is to improve these drugs and investigate how they counteract injury. ..
  17. Renal Angiotensin II Receptor Function in Obesity
    Tahir Hussain; Fiscal Year: 2013
    ..We propose to investigate the role of a novel target, namely the Angiotensin II AT2 receptor, to improve kidney function and lower blood pressure in an obesity/diabetic animal model. ..
  18. Regulation of Neuronal Survival by the Rit GTPase
    DOUGLAS ALLEN ANDRES; Fiscal Year: 2012
    ..Thus, the goal of this research is to speed progress toward therapeutic exploitation of this protein in neurodegenerative disease. ..
  19. Cardiovascular effects of GLP-1 in obesity/metabolic syndrome
    Johnathan D Tune; Fiscal Year: 2013
    ..Further, these studies will accelerate discovery of new therapeutic targets or strategies that could substantially improve the cardioprotective efficacy of GLP-1 based therapies in patients with obesity-related cardiovascular disease. ..
  20. MECHANISMS OF CHONDROPROTECTION BY POMEGRANATE FRUIT EXTRACT
    Tariq M Haqqi; Fiscal Year: 2011
    ..Our findings may open new avenues regarding the use of PFE or compounds derived from it for the treatment and/or prevention of OA. ..
  21. Mechanism of Neutrophil Activation
    Kenneth R McLeish; Fiscal Year: 2013
    ..Thus, new approaches to treating Veteran patients with a number of acute and chronic inflammatory diseases are anticipated. ..
  22. The Role of Kappa Opioid Receptor-induced Activation of Astrocytes in the Reinsta
    Charles Chavkin; Fiscal Year: 2009
    ..This study would identify the connection between astrocyte activation and reinstatement of extinguished cocaine place preference by assessing the effects of selectively disrupting kappa opioid signaling in astroctyes on behavior. ..
  23. Mitogen-activated Protein Kinases and NF-kB Activation in Vascular Smooth Muscle
    Bingbing Jiang; Fiscal Year: 2010
    ....
  24. INFLAMMATORY RESPONSES IN THE TOXICITY OF RICIN
    Bruce Magun; Fiscal Year: 2009
    ....
  25. The Role of Xanthine Oxidoreductase in Ventilator-Associated Lung Injury
    Paul M Hassoun; Fiscal Year: 2013
    ....
  26. Molecular Mechanisms and Treatment of Primary Amyloid AL Cardiomyopathy
    Ronglih Liao; Fiscal Year: 2013
    ..This work represents our continued intensive investigation of the mechanism underlying amyloid cardiomyopathy. ..
  27. ETHANOL REGULATION OF KUPFFER CELL SIGNAL TRANSDUCTION
    Laura E Nagy; Fiscal Year: 2013
    ....
  28. Effects of Macronutrients on Regulation of Endoplasmic Reticulum Stress in Human
    Guenther Boden; Fiscal Year: 2013
    ..Therefore, it is important to understand how obesity is linked with IR and IF. In the proposed studies we will examine how excess nutrient intake, the major cause for obesity, can acutely produce IR and IF. ..
  29. Exercise Induced Biochemical and Anatomical Adaptations
    John O Holloszy; Fiscal Year: 2013
    ..abstract_text> ..
  30. Small heat shock proteins in smooth muscle plasticity
    William T Gerthoffer; Fiscal Year: 2013
    ..Discovering how this pathway can alter the function of microRNAs could lead to new anti-inflammatory drugs or combinations of drugs to treat lung diseases more effectively. ..
  31. THE STRESS-ACTIVATED PROTEIN KINASE PATHWAY
    John M Kyriakis; Fiscal Year: 2010
    ..These studies will provide important details of a previously unknown signaling pathway required for inflammatory responses. ..
  32. Regulation of Obesity by the Alpha-arrestin ARRDC3
    Ronald B Myers; Fiscal Year: 2013
    ..The insights from the proposed research are critically important to the design of successful treatments and preventative measures against obesity. ..
  33. Role of Cholesterol in Age-related Decline in Steroidogenesis
    Salman Azhar; Fiscal Year: 2013
    ....
  34. p38 MAP kinase in early thymocyte development
    Mercedes Rincon; Fiscal Year: 2013
    ..In addition, genetic mutations that may affect this pathway could determine a relatively higher susceptibility to develop T cell malignancies. ..
  35. Cardiomyocyte Apoptosis and Cardioprotective Actions of Estrogen
    Jin Kyung Kim; Fiscal Year: 2013
    ....
  36. Alcohol-Induced Fatty Liver and Injury in Humanized CYP2E1 Knockin Mice.
    Arthur I Cederbaum; Fiscal Year: 2011
    ..Identification of downstream effectors of alcohol/CYP2E1 actions would be very informative in developing therapeutic interventions against alcohol-induced liver injury and fatty liver. ..
  37. CARP-1: A Potential Therapeutic Agent for Breast Cancer
    ARUN KUMAR RISHI; Fiscal Year: 2013
    ..abstract_text> ..
  38. A Study of Biological Function of Basonuclin
    George Cotsarelis; Fiscal Year: 2010
    ..The role of Bnc's in the EGFr pathway will be discerned. The studies will impact on understanding stem cell biology and the role of Bnc's in wound healing, hair cycling and skin regeneration. ..
  39. Epidemic Typhus Pathogenesis
    Sanjeev K Sahni; Fiscal Year: 2010
    ..prowazekii, to expand our understanding of in vivo host immune responses, and to test the efficacy of novel antibiotics and vaccine candidates. ..
  40. Targeting the ROS-p38 MAPK Pathway as a Novel Strategy for Stem Cell Expansion
    GAVIN YONG WANG; Fiscal Year: 2012
    ..Such information will be essential to the development of innovative culture strategies for the ex vivo expansion of HSCs. ..
  41. NGF Receptor Regulates Prostate Growth
    Daniel Djakiew; Fiscal Year: 2009
    ..By lead compound optimization, we anticipate the development of novel chemotherapeutics with a novel mechanism of action for the treatment of prostate cancer. ..
  42. Orexin Induced Gene and Protein Expression Patterns in the rLH
    TAMMY ANGALINE BUTTERICK; Fiscal Year: 2013
    ..This mechanism may be responsible for conferring long-term obesity resistance and would provide a new therapeutic target for obesity. ..
  43. p38 MAPK as a female-specific druggable target in CNS autoimmune disease
    Cory Teuscher; Fiscal Year: 2012
    ....
  44. MECHANISM OF CANALICULAR BILE FORMATION AND CHOLESTASIS
    MOHAMMED SAWKAT ANWER; Fiscal Year: 2010
    ..By defining the isoforms that are involved in the cholestatic effect, we should be able to design therapeutic agents that selectively reverse cholestatic effect without affecting beneficial effects. ..
  45. p38 MAPK Mechanisms of Kappa Opioid-Induced Aversion
    Charles Chavkin; Fiscal Year: 2013
    ....
  46. EFFECTS OF ACID ON BONE
    David A Bushinsky; Fiscal Year: 2010
    ..The current proposal is aimed at understanding the first steps by which acid is detected by bone cells. Understanding the process by which the bone detects and neutralizes the acid can lead to an improvement in bone health. ..
  47. p38 MAPK a regulator of muscle contraction and function
    Zhen Yan; Fiscal Year: 2013
    ....
  48. DIFFERENTIATING AGENTS IN HEMATOLOGIC MALIGNANCIES
    Donald W Kufe; Fiscal Year: 2012
    ..The proposed work will expand our understanding of how agents that disrupt redox balance induce terminal differentiation in the laboratory and in patients on clinical trials. ..
  49. Oxidative Stress, Mitochondrial Dysfunction and Aging
    JOHN NMN PAPACONSTANTINOU; Fiscal Year: 2010
    ..abstract_text> ..
  50. Myocardial Adenosine Receptors
    James G Dobson; Fiscal Year: 2010
    ..Such information should be instrumental for the development of new therapies and agents to alleviate cardiac dysfunction. ..
  51. Neuroprotection in Models of Cerebral Ischemia
    Jun Chen; Fiscal Year: 2013
    ..A positive outcome of the project not only will have a high impact on enhancing our understanding of the basic molecular mechanisms of ischemic neuronal injury but also shed light on ASK1 as a potential therapeutic target for stroke. ..
  52. Signaling and microRNA function in neurons
    David L Turner; Fiscal Year: 2012
    ....
  53. Molecular basis of homocysteine-glutamate receptor mediated neuronal cell death
    Ranjana Poddar; Fiscal Year: 2012
    ..Understanding these novel molecular events triggered by homocysteine may facilitate development of targeted therapeutic approaches to reduce brain damage associated with neurodegenerative disorders in hyper-homocysteinemic individuals. ..
  54. MECHANISMS OF CORONARY FLOW REGULATION BY ADENOSINE
    S Jamal Mustafa; Fiscal Year: 2013
    ..This project will utilize all four single and double AR gene deleted mice to understand the signaling pathways for each AR subtype. ..
  55. Stress resistance in neurons from primate iPS cells
    Peter J Hornsby; Fiscal Year: 2013
    ..These experiments will allow, for the first time, direct comparisons of stress resistance in isolated neurons from different species and will provide new insights into the mechanisms by which species differ in longevity. ..
  56. Mechanism of Anthrax Lethal Factor Toxicity
    Usamah S Kayyali; Fiscal Year: 2012
    ..Furthermore, we expect our experiments to show that targeting HSP27 phosphorylation is a mechanistically sound approach to treat anthrax and to demonstrate the effectiveness of that approach in animal models of anthrax. ..
  57. Transgenic Mouse Model to Address Heterogeneity in Autism Spectrum Disorders
    RANDY DEAN BLAKELY; Fiscal Year: 2010
    ..Based on exciting preliminary evidence that mice expressing Ala56 SERT exhibit multiple behavioral and biochemical phenotypes, we propose a two-year project to extend our studies and dissect the impact of SERT hyperfunction in vivo. ..
  58. Reactive Oxygen Species in Coronary Collateral Growth
    William M Chilian; Fiscal Year: 2013
    ..These studies will provide insight into the cell-specific locations where ROS and redox signaling modulate coronary collateral growth. ..
  59. NEUROCHEMICAL MECHANISMS OF VISCERAL PAIN
    Richard J Traub; Fiscal Year: 2013
    ..Public Health Relevance ..
  60. MAP Kinase Signaling in Apoptosis-Induced Ventilator-Associated Lung Injury
    Mahendra Damarla; Fiscal Year: 2013
    ..We have identified a pathway and a potential mechanism that is relevant in mediating injury due to mechanical ventilation. We hope that further insight will help identify novel therapeutic targets...
  61. Post-transcriptional control of inflammatory gene expression
    Thomas A Hamilton; Fiscal Year: 2013
    ..This proposal is focused upon understanding the mechanisms through which IL-17 (and other stimuli) controls degradation of specific inflammation related messenger RNAs and thereby modulates aspects of inflammatory response. ..
  62. Fibrosis-Protease Cross-Talk Regulating Pancreatic Cancer Invasion
    Hidayatullah G Munshi; Fiscal Year: 2013
    ..abstract_text> ..
  63. Transcription & Function of Adipocyte Beta3AR in Obesity
    Sheila Collins; Fiscal Year: 2006
    ..abstract_text> ..
  64. Role of p38 MAPK in IL-4-induced IL-6 expression in vascular endothelium
    Yongwoo Lee; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  65. Macrophage Foam Cells, Cathepsins and Cholesterol Efflux
    ALAN RICHARD TALL; Fiscal Year: 2010
    ..These mechanistic insights may suggest new treatments for vulnerable human plaques such as LXR activators, CatK inhibitors or inhibitors of RANK signaling. ..
  66. ERYTHROPOIETIN AND THE REGULATION OF ERYTHROPOIESIS
    Sanford Krantz; Fiscal Year: 2003
    ..These experiments have direct application to understanding the anemia of chronic disease and the increased apoptosis in MDS, which produces a marked decrease in human blood cells. ..
  67. STRETCH-INDUCED CYCLOOXYGENASE-2 IN UROTHELIAL CELLs
    Stephen Nakada; Fiscal Year: 2005
    ..abstract_text> ..
  68. Aberrant kinase signaling in cholangiocarcinoma
    Tushar Patel; Fiscal Year: 2003
    ..This information will ultimately contribute to the development of specific therapies for biliary tract malignancies, as well as interventions to treat or prevent neoplasia during chronic inflammation. ..
  69. Novel Bioactive Lipid Receptors in Growth Regulation
    Yan Xu; Fiscal Year: 2005
    ..These studies may lead to novel therapies to treat highly malignant ovarian cancer, as well as other tumors. ..