P R Young

Summary

Affiliation: SmithKline Beecham Pharmaceuticals
Country: USA

Publications

  1. ncbi request reprint Pharmacological modulation of cytokine action and production through signaling pathways
    P R Young
    Department of Molecular Biology UW2101, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa 19406 0939, USA
    Cytokine Growth Factor Rev 9:239-57. 1998
  2. ncbi request reprint Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site
    P R Young
    Department of Comparative Genetics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406 0939, USA
    J Biol Chem 272:12116-21. 1997
  3. ncbi request reprint Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles
    S Kumar
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406 0939, USA
    Biochem Biophys Res Commun 235:533-8. 1997
  4. ncbi request reprint 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
  5. ncbi request reprint Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines
    J A Harrop
    Department of Molecular and Cellular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA
    J Immunol 161:1786-94. 1998
  6. ncbi request reprint Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli
    S Kumar
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    Biochem Biophys Res Commun 235:474-8. 1997
  7. ncbi request reprint Identification of two distinct regions of p38 MAPK required for substrate binding and phosphorylation
    R J Gum
    Department of Molecular Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA19406, USA
    Biochem Biophys Res Commun 266:284-9. 1999
  8. ncbi request reprint Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase
    M M McLaughlin
    Department of Gene Expression Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 271:8488-92. 1996
  9. ncbi request reprint Identification and initial characterization of four novel members of the interleukin-1 family
    S Kumar
    Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 275:10308-14. 2000
  10. ncbi request reprint Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth
    J A Harrop
    Department of Molecular and Cellular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 273:27548-56. 1998

Collaborators

Detail Information

Publications32

  1. ncbi request reprint Pharmacological modulation of cytokine action and production through signaling pathways
    P R Young
    Department of Molecular Biology UW2101, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa 19406 0939, USA
    Cytokine Growth Factor Rev 9:239-57. 1998
    ..This review summarizes the current state of knowledge about several of these pathways, how they regulate cytokine action or production, and their potential for pharmacological intervention...
  2. ncbi request reprint Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site
    P R Young
    Department of Comparative Genetics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406 0939, USA
    J Biol Chem 272:12116-21. 1997
    ....
  3. ncbi request reprint Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles
    S Kumar
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406 0939, USA
    Biochem Biophys Res Commun 235:533-8. 1997
    ..These data suggest that SAPK3 and SAPK4 form a distinct subset of the p38 MAP kinases with different expression pattern, response to stimuli, substrate specificity, and inhibitor sensitivity...
  4. ncbi request reprint 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...
  5. ncbi request reprint Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines
    J A Harrop
    Department of Molecular and Cellular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA
    J Immunol 161:1786-94. 1998
    ..In conclusion, these results suggest that TR2 is involved in the activation cascade of T cell responses and TR2 mAbs prevent optimal T cell proliferation, cytokine production, and expression of activation markers...
  6. ncbi request reprint Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli
    S Kumar
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    Biochem Biophys Res Commun 235:474-8. 1997
    ..The expression of the membrane ST2, however, remained constant. These data suggest a role for ST2 in inflammation...
  7. ncbi request reprint Identification of two distinct regions of p38 MAPK required for substrate binding and phosphorylation
    R J Gum
    Department of Molecular Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA19406, USA
    Biochem Biophys Res Commun 266:284-9. 1999
    ..Hence, we show for the first time that MAPKs contain two distinct regions for recognizing and phosphorylating protein substrates...
  8. ncbi request reprint Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase
    M M McLaughlin
    Department of Gene Expression Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 271:8488-92. 1996
    ..These data suggest that MAPKAP kinase-3 is activated by stress and cytokines and is a novel substrate of CSBP both in vitro and in vivo...
  9. ncbi request reprint Identification and initial characterization of four novel members of the interleukin-1 family
    S Kumar
    Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 275:10308-14. 2000
    ..This suggests that IL-1H1 may be involved in pathogenesis of immune mediated disease processes. The addition of four novel IL-1 homologues suggests that the IL-1 family is significantly larger than previously thought...
  10. ncbi request reprint Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth
    J A Harrop
    Department of Molecular and Cellular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 273:27548-56. 1998
    ..A soluble, secreted form of the protein stimulates proliferation of T lymphocytes during allogeneic responses, inhibits HT-29 cell growth, and weakly stimulates NF-kappaB-dependent transcription...
  11. ncbi request reprint Localization of the human stress responsive MAP kinase-like CSAIDs binding protein (CSBP) gene to chromosome 6q21.3/21.2
    P C McDonnell
    Department of Molecular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    Genomics 29:301-2. 1995
  12. ncbi request reprint Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration
    J R White
    Department of Molecular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 273:10095-8. 1998
    ..This selective antagonist will be a useful tool compound to define the role of CXCR2 in inflammatory diseases where neutrophils play a major role...
  13. ncbi request reprint Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL
    J G Emery
    Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 273:14363-7. 1998
    ..OPG inhibits TRAIL-induced apoptosis of Jurkat cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These data suggest potential cross-regulatory mechanisms by OPG and TRAIL...
  14. ncbi request reprint Human mitogen-activated protein kinase CSBP1, but not CSBP2, complements a hog1 deletion in yeast
    S Kumar
    Department of Molecular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 270:29043-6. 1995
    ....
  15. ncbi request reprint ST2/T1 protein functionally binds to two secreted proteins from Balb/c 3T3 and human umbilical vein endothelial cells but does not bind interleukin 1
    S Kumar
    Department of Molecular Immunology, SmithKline Beecham Research and Development, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 270:27905-13. 1995
    ..The putative ligand was also able to stimulate CSBP/p38 MAP kinase through the ST2 receptor. These results suggest that the ST2 is not an IL-1 receptor but rather has its own cognate ligand...
  16. ncbi request reprint Structural basis of inhibitor selectivity in MAP kinases
    Z Wang
    Department of Biochemistry The University of Texas Southwestern Medical Center at Dallas 5323 Harry Hines Boulevard, Dallas, TX 75235, USA
    Structure 6:1117-28. 1998
    ..Although these compounds are known to bind to the ATP-binding site, the origin of the inhibitory specificity toward p38 is not clear...
  17. ncbi request reprint A new nomenclature for IL-1-family genes
    J E Sims
    Trends Immunol 22:536-7. 2001
  18. ncbi request reprint Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors
    D Leung
    Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
    J Biol Chem 276:45762-71. 2001
    ..Aprotinin was the only standard serine protease inhibitor to be active, whereas a number of peptide substrate analogues were found to be competitive inhibitors at micromolar concentrations...
  19. ncbi request reprint Homology model of the dengue 2 virus NS3 protease: putative interactions with both substrate and NS2B cofactor
    R I Brinkworth
    Centre for Drug Design and Development, University of Queensland, St Lucia, Brisbane, Australia
    J Gen Virol 80:1167-77. 1999
    ....
  20. ncbi request reprint Substrate specificity of recombinant dengue 2 virus NS2B-NS3 protease: influence of natural and unnatural basic amino acids on hydrolysis of synthetic fluorescent substrates
    I E Gouvea
    Departmento de Biofisica, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Rua Tres de Maio, 100 São Paulo 04044 020, Brazil
    Arch Biochem Biophys 457:187-96. 2007
    ....
  21. ncbi request reprint The yeast FKS1 gene encodes a novel membrane protein, mutations in which confer FK506 and cyclosporin A hypersensitivity and calcineurin-dependent growth
    W K Eng
    Department of Biomolecular Disovery, SmithKline Beecham Pharmaceuticals King of Prussia, PA 19406
    Gene 151:61-71. 1994
    ..These data suggest that FKS1 provides a unique cellular function which, when absent, increases FK506 and CsA sensitivity by making the CNs (or a CN-dependent function) essential...
  22. ncbi request reprint Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3
    A Ben-Baruch
    Laboratory of Molecular Immunoregulation, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA
    J Biol Chem 270:22123-8. 1995
    ..Since MCP3 has been reported to use MCP1 receptor(s), our results with transfected 293 cells expressing only C-C CKR1 clearly establish that C-C CKR1 is also a functional receptor for MCP3...
  23. pmc Soluble type II interleukin 1 (IL-1) receptor binds and blocks processing of IL-1 beta precursor and loses affinity for IL-1 receptor antagonist
    J A Symons
    Department of Medicine, University of Sheffield, Royal Hallamshire Hospital, United Kingdom
    Proc Natl Acad Sci U S A 92:1714-8. 1995
    ..In addition, type II sIL-1R does not interfere with inhibition mediated by IL-1ra...
  24. ncbi request reprint A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress
    A D Clifton
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Scotland, UK
    FEBS Lett 392:209-14. 1996
    ..These results establish that MAPKAP kinase-3 lies 'downstream' of SAPK-2 and that it is likely to have overlapping or identical substrates to MAPKAP kinase-2 in vivo...
  25. ncbi request reprint Hemopoietic growth factors with the exception of interleukin-4 activate the p38 mitogen-activated protein kinase pathway
    I N Foltz
    The Biomedical Research Centre, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 272:3296-301. 1997
    ..These findings demonstrate that the activation of p38 MAP kinase is involved not only in responses to stresses but also in signaling by growth factors that regulate the normal development and function of cells of the immune system...
  26. ncbi request reprint Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication
    J M MacKenzie
    Sir Albert Sakzewski Virus Research Centre, Royal Children s Hospital, Brisbane, Australia
    Virology 220:232-40. 1996
    ..These findings provide further insights into the maturation pathway of NS1 and suggest a possible role for this protein in viral RNA replication...
  27. ncbi request reprint Amino acid sequence of a novel protein phosphatase 1 binding protein (R5) which is related to the liver- and muscle-specific glycogen binding subunits of protein phosphatase 1
    M J Doherty
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Scotland, UK
    FEBS Lett 399:339-43. 1996
    ..The amino acid sequence and properties of PPP1R5 indicate that it is not subject to the same modes of covalent and allosteric regulation by hormones as are G(M) and G(L)...
  28. ncbi request reprint Dengue virus nonstructural protein 1 is expressed in a glycosyl-phosphatidylinositol-linked form that is capable of signal transduction
    M G Jacobs
    Department of Paediatrics, Imperial College School of Medicine, Norfolk Place, London W2 1PG, U K
    FASEB J 14:1603-10. 2000
    ..Signal transduction by a GPI-anchored viral antigen interacting with a specific antibody that it induces is a new concept in the pathogenesis of viral disease...
  29. pmc Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain
    K Ozaki
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Proc Natl Acad Sci U S A 97:11439-44. 2000
    ..This finding suggests that NILR has signaling potential but that a full understanding of its signaling partner(s) is not yet clear. Like IL-2Rbeta, NILR associates with Jak1 and mediates Stat5 activation...
  30. ncbi request reprint A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation
    B S Kwon
    Department of Microbiology and Immunology and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 272:14272-6. 1997
    ..A TR2-Fc fusion protein inhibited a mixed lymphocyte reaction-mediated proliferation suggesting that the receptor and/or its ligand play a role in T cell stimulation...
  31. ncbi request reprint Cloning of rabbit interleukin-1 beta: differential evolution of IL-1 alpha and IL-1 beta proteins
    P R Young
    Department of Molecular Genetics, Smith Kline and French Laboratories, King of Prussia, Pa 19406 0939
    Protein Eng 2:545-51. 1989
    ..These differences may therefore provide an explanation for the existence of two IL-1 molecules...
  32. ncbi request reprint Production of dimer-specific and dengue virus group cross-reactive mouse monoclonal antibodies to the dengue 2 virus non-structural glycoprotein NS1
    A K Falconar
    Wolfson Molecular Biology Unit, London School of Hygiene and Tropical Medicine, U K
    J Gen Virol 72:961-5. 1991
    ....