J Downward

Summary

Affiliation: Imperial Cancer Research Fund
Country: UK

Publications

  1. ncbi request reprint Cell cycle: routine role for Ras
    J Downward
    Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Curr Biol 7:R258-60. 1997
  2. ncbi request reprint Mechanisms and consequences of activation of protein kinase B/Akt
    J Downward
    Imperial Cancer Research Fund, London, UK
    Curr Opin Cell Biol 10:262-7. 1998
  3. ncbi request reprint Ras signalling and apoptosis
    J Downward
    Imperial Cancer Research Fund, London, UK
    Curr Opin Genet Dev 8:49-54. 1998
  4. ncbi request reprint Akt/PKB localisation and 3' phosphoinositide generation at sites of epithelial cell-matrix and cell-cell interaction
    S J Watton
    Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Curr Biol 9:433-6. 1999
  5. pmc Analysis of the transcriptional program induced by Raf in epithelial cells
    A Schulze
    Signal Transduction Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK
    Genes Dev 15:981-94. 2001
  6. ncbi request reprint Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras
    P Rodriguez-Viciana
    Imperial Cancer Research Fund, London, United Kingdom
    Cell 89:457-67. 1997
  7. pmc Raf induces TGFbeta production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells
    K Lehmann
    Signal Transduction, Imperial Cancer Research Fund, London WC2A 3PX, UK
    Genes Dev 14:2610-22. 2000
  8. pmc Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation
    P Rodriguez-Viciana
    Imperial Cancer Research Fund, London
    EMBO J 15:2442-51. 1996
  9. ncbi request reprint Networks of interaction of p120cbl and p130cas with Crk and Grb2 adaptor proteins
    A Khwaja
    Imperial Cancer Research Fund, London, UK
    Oncogene 12:2491-8. 1996
  10. ncbi request reprint Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro
    P H Warne
    Imperial Cancer Research Fund, London, UK
    Nature 364:352-5. 1993

Collaborators

Detail Information

Publications37

  1. ncbi request reprint Cell cycle: routine role for Ras
    J Downward
    Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Curr Biol 7:R258-60. 1997
    ..The Ras proteins are key mediators of the early cellular response to mitogens; the way in which they influence the later events in the cell cycle is beginning to fall into place...
  2. ncbi request reprint Mechanisms and consequences of activation of protein kinase B/Akt
    J Downward
    Imperial Cancer Research Fund, London, UK
    Curr Opin Cell Biol 10:262-7. 1998
    ..Activated PKB/Akt provides a survival signal that protects cells from apoptosis induced by various stresses, and also mediates a number of metabolic effects of insulin...
  3. ncbi request reprint Ras signalling and apoptosis
    J Downward
    Imperial Cancer Research Fund, London, UK
    Curr Opin Genet Dev 8:49-54. 1998
    ..Recently Ras has been shown to be able to protect cells from apoptosis either through activation of PKB/Akt via PI3-kinase, or through activation of NF-kappa B...
  4. ncbi request reprint Akt/PKB localisation and 3' phosphoinositide generation at sites of epithelial cell-matrix and cell-cell interaction
    S J Watton
    Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Curr Biol 9:433-6. 1999
    ..We propose that the attachment-induced, PI-3-kinase-mediated survival signal in epithelial cells is generated not only by cell-matrix interaction but also by cell-cell interaction...
  5. pmc Analysis of the transcriptional program induced by Raf in epithelial cells
    A Schulze
    Signal Transduction Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK
    Genes Dev 15:981-94. 2001
    ....
  6. ncbi request reprint Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras
    P Rodriguez-Viciana
    Imperial Cancer Research Fund, London, United Kingdom
    Cell 89:457-67. 1997
    ..The ability of activated Ras to stimulate PI 3-kinase in addition to Raf is therefore important in Ras transformation of mammalian cells and essential in Ras-induced cytoskeletal reorganization...
  7. pmc Raf induces TGFbeta production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells
    K Lehmann
    Signal Transduction, Imperial Cancer Research Fund, London WC2A 3PX, UK
    Genes Dev 14:2610-22. 2000
    ..The Raf-MAP kinase pathway thus synergizes with TGFbeta in promoting malignancy but does not directly impair TGFbeta-induced Smad signaling...
  8. pmc Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation
    P Rodriguez-Viciana
    Imperial Cancer Research Fund, London
    EMBO J 15:2442-51. 1996
    ..These data show that PI 3-kinase is regulated by a number of mechanisms, and that Ras contributes to the activation of this lipid kinase synergistically with tyrosine kinases...
  9. ncbi request reprint Networks of interaction of p120cbl and p130cas with Crk and Grb2 adaptor proteins
    A Khwaja
    Imperial Cancer Research Fund, London, UK
    Oncogene 12:2491-8. 1996
    ..These data indicate that adaptor proteins can exchange binding partners in response to stimuli, and that different adaptor proteins can bind to the same partners by different mechanisms...
  10. ncbi request reprint Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro
    P H Warne
    Imperial Cancer Research Fund, London, UK
    Nature 364:352-5. 1993
    ..In addition, Raf itself displays weak GTPase-stimulating activity towards Ras. It is therefore likely that Raf is a direct effector of Ras...
  11. ncbi request reprint Trachealess--a new transcription factor target for PKB/Akt
    J Downward
    Signal Transduction Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Dev Cell 1:726-8. 2001
    ..Applying a combined genetic and biochemical approach has led to the identification of a new protein kinase B/Akt target, the transcription factor Trachealess...
  12. ncbi request reprint Interaction of F1L with the BH3 domain of Bak is responsible for inhibiting vaccinia-induced apoptosis
    A Postigo
    Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cell Death Differ 13:1651-62. 2006
    ..We also find that such additional BH3-like domains exist in the vaccinia genome. We conclude that F1L uses this specific, BH3-like domain to bind and inhibit Bak at the mitochondria...
  13. doi request reprint Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells
    Y Wang
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Oncogene 29:4658-70. 2010
    ....
  14. doi request reprint An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis
    R Lara
    Department of Oncology, Hammersmith Campus, Cyclotron Building, London, UK
    Oncogene 30:3513-21. 2011
    ..Our results suggest that the findings of our high-throughput in vitro screen can reliably identify relevant clinical targets and as a proof of principle, RSK1 may provide a biomarker for metastasis in lung cancer patients...
  15. ncbi request reprint Interaction of Ras and Raf in intact mammalian cells upon extracellular stimulation
    B Hallberg
    Imperial Cancer Research Fund, London, United Kingdom
    J Biol Chem 269:3913-6. 1994
    ..Specific interaction of Ras and Raf therefore occurs in intact mammalian cells in response to stimuli that cause Ras to become GTP-bound...
  16. doi request reprint PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs
    B Weigelt
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Oncogene 30:3222-33. 2011
    ....
  17. doi request reprint Viral pro-survival proteins block separate stages in Bax activation but changes in mitochondrial ultrastructure still occur
    J R Cross
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cell Death Differ 15:997-1008. 2008
    ..We suggest that the ability of mitochondria to respond to apoptotic stress prior to Bax activation indicates that these organelles may play a direct role in activating Bax...
  18. doi request reprint Rictor is a novel target of p70 S6 kinase-1
    C Treins
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Oncogene 29:1003-16. 2010
    ..These findings reveal an unexpected signaling input into mTORC2, which is regulated by amino acids, growth factors and rapamycin...
  19. ncbi request reprint Upregulation of two BH3-only proteins, Bmf and Bim, during TGF beta-induced apoptosis
    A R Ramjaun
    1Signal Transduction, Cancer Research UK London Research Institute, London, UK
    Oncogene 26:970-81. 2007
    ..The TGFbeta-triggered cell death programme thus involves induction of multiple BH3-only proteins during the induction of apoptosis...
  20. ncbi request reprint Regulation of MUC1 expression in human mammary cell lines by the c-ErbB2 and ras signaling pathways
    A G Scibetta
    Imperial Cancer Resarch Fund, Breast Cancer Biology Group, Thomas Guy House, Guy's Hospital, London, UK
    DNA Cell Biol 20:265-74. 2001
    ....
  21. ncbi request reprint Functional inhibition of PI3K by the betaGBP molecule suppresses Ras-MAPK signalling to block cell proliferation
    V Wells
    Cell Signalling and Growth Laboratory, Pharmaceutical Science Research Division, King s College London, London, UK
    Oncogene 26:7709-14. 2007
    ..This study sheds light on the molecular mechanisms whereby betaGBP can control cell proliferation and, by extension, may potentially control tumorigenesis by controlling PI3K...
  22. ncbi request reprint Navigating gene expression using microarrays--a technology review
    A Schulze
    Signal Transduction Laboratory, Imperial Cancer Research Fund, 44Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Cell Biol 3:E190-5. 2001
    ..This should allow new understanding of signalling networks that operate in the cell and of the molecular basis and classification of disease. But can the technology deliver such far-reaching promises?..
  23. ncbi request reprint Analysis of gene expression by microarrays: cell biologist's gold mine or minefield?
    A Schulze
    Signal Transduction Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK
    J Cell Sci 113:4151-6. 2000
    ....
  24. pmc Evaluation of epidermal growth factor receptors in bladder tumours
    M S Berger
    Imperial Cancer Research Fund Laboratories, Lincoln s Inn Fields, London, UK
    Br J Cancer 56:533-7. 1987
    ....
  25. ncbi request reprint Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain
    V Cowling
    Signal Transduction Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cell Death Differ 9:1046-56. 2002
    ..We suggest that the requirement for two distinct cleavage steps to activate an effector caspase may represent an effective mechanism for restriction of spontaneous caspase activation and aberrant entry into apoptosis...
  26. ncbi request reprint Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling
    U K Khanzada
    Lung Cancer Biology Group, Division of Medicine, Imperial College Faculty of Medicine, Hammersmith Hospital, London, UK
    Oncogene 25:877-87. 2006
    ..Together our data demonstrate that inhibiting Ras signalling with simvastatin potently disrupts growth and survival in human SCLC cells...
  27. ncbi request reprint SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases
    K Reif
    Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, Lincolns Inn Fields, London, United Kingdom
    J Biol Chem 269:14081-7. 1994
    ..It is thus possible to speculate that the interaction of either p75 or Sos with the Grb2 SH3 domain may influence the interaction of the Grb2 SH2 domain with tyrosine phosphoproteins...
  28. ncbi request reprint The activation of phosphatidylinositol 3-kinase by Ras
    T Kodaki
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    Curr Biol 4:798-806. 1994
    ..Recent evidence indicates that Ras can bind to the p85 alpha/p110 alpha complex. We describe here the functional regulation of the mammalian phosphatidylinositol 3-kinase complex by Ras...
  29. ncbi request reprint Role of Shc in the activation of Ras in response to epidermal growth factor and nerve growth factor
    T Basu
    Imperial Cancer Research Fund, London, UK
    Oncogene 9:3483-91. 1994
    ....
  30. ncbi request reprint Apoptosis: Ras to the rescue in the fly eye
    H McNeill
    Developmental Patterning Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Curr Biol 9:R176-9. 1999
    ..Recent results on the way Ras and downstream pathways can influence cell-death induction suggest the regulatory pathways in these distinct organisms might be more similar than was at first sight apparent...
  31. ncbi request reprint Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells
    P S Costello
    National Institute for Medical Research, London, UK
    Oncogene 13:2595-605. 1996
    ..A similar mechanism is likely to apply to signal transduction through all members of the antigen receptor family...
  32. ncbi request reprint The effector loop and prenylation site of R-Ras are involved in the regulation of integrin function
    B Oertli
    Department of Vascular Biology, The Scripps Research Institute, La Jolla, California, CA 92037, USA
    Oncogene 19:4961-9. 2000
    ..Consequently, these studies provide insight into the structural basis of the interactions between R-Ras and its candidate effectors and suggest the existence of novel mechanisms through which this GTPase could regulate cell adhesion...
  33. pmc P110delta, a novel phosphoinositide 3-kinase in leukocytes
    B Vanhaesebroeck
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, United Kingdom
    Proc Natl Acad Sci U S A 94:4330-5. 1997
    ..Possible selective functions of p110delta in white blood cells are discussed...
  34. ncbi request reprint Murine Ksr interacts with MEK and inhibits Ras-induced transformation
    A Denouel-Galy
    Unité Mixte de Recherche 146 du CNRS Institut Curie Centre Universitaire Laboratoire 110 91405, Orsay Cedex, France
    Curr Biol 8:46-55. 1998
    ..To investigate whether these structural similarities correlated with common functional properties, we examined the ability of mKsr-1, the murine homolog of Ksr, to interact with components of the vertebrate MAP kinase pathway...
  35. ncbi request reprint Identification of the ras GTPase-activating protein GAP1(m) as a phosphatidylinositol-3,4,5-trisphosphate-binding protein in vivo
    P J Lockyer
    Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
    Curr Biol 9:265-8. 1999
    ..From these results, we conclude that GAP1(m) binds PIP3 in vivo, and it is recruited to the plasma membrane, but does not appear to be activated, following agonist stimulation of PI 3-kinase...
  36. ncbi request reprint Farnesylation of Ras is important for the interaction with phosphoinositide 3-kinase gamma
    I Rubio
    Research Unit Molecular Cell Biology, Medical Faculty, Friedrich Schiller University, Jena, Germany
    Eur J Biochem 266:70-82. 1999
    ..The results suggest a direct interaction between a moiety present only on fully processed or farnesylated Ras and the putative target protein p110gamma...
  37. pmc Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor
    S Wennström
    Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
    Mol Cell Biol 19:4279-88. 1999
    ....