proto oncogene proteins c raf

Summary

Summary: A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.

Top Publications

  1. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
  2. ncbi The RAF proteins take centre stage
    Claudia Wellbrock
    Signal Transduction Team, Cancer Research UK Centre of Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nat Rev Mol Cell Biol 5:875-85. 2004
  3. pmc Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions
    W Kolch
    The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, U K
    Biochem J 351:289-305. 2000
  4. ncbi C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB
    Sonja I Gringhuis
    Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
    Immunity 26:605-16. 2007
  5. pmc Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma
    Clara Montagut
    Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, USA
    Cancer Res 68:4853-61. 2008
  6. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
  7. ncbi BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis
    Scott M Wilhelm
    Bayer Pharmaceuticals Corporation, West Haven, Connecticut 06516, USA
    Cancer Res 64:7099-109. 2004
  8. pmc B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts
    Catrin A Pritchard
    Department of Biochemistry, University of Leicester, United Kingdom
    Mol Cell Biol 24:5937-52. 2004
  9. ncbi Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes
    Aki Fujioka
    Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita Shi, Osaka 565 0871, Japan
    J Biol Chem 281:8917-26. 2006
  10. ncbi Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP
    K Yeung
    Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Richmond 02912, USA
    Nature 401:173-7. 1999

Research Grants

  1. REGULATION OF THE SENSITIVITY OF DOPAMINE RECEPTORS
    KIM ARTHUR NEVE; Fiscal Year: 2013
  2. Neurochemical Basis of Opiate Addiction
    HORACE LOH; Fiscal Year: 2013
  3. INTERACTIONS OF MYOTONIC DYSTROPHY PROTEIN KINASE
    Henry Epstein; Fiscal Year: 2004
  4. Protein inhibitor of Raf-1 kinase
    Kam Yeung; Fiscal Year: 2005
  5. RAS CAAX PEPTIDOMIMETICS IN PULMONARY INFLAMMATION
    Jonathan Finder; Fiscal Year: 2000
  6. ROLE OF RAF IN RAS TRANSFORMATION
    Sharon Campbell; Fiscal Year: 2000
  7. ETHANOL, NEURAL DIFFERENTIATION, AND PROTEIN KINASE C
    Robert Messing; Fiscal Year: 1999
  8. KINASE ENCODING PROTO-ONCOGENES IN IL-2 SIGNAL TRANSDUCT
    John Reed; Fiscal Year: 1993
  9. CHEMOKINE RECEPTORS AND HIV MEDIATED SIGNALING
    Waldemar Popik; Fiscal Year: 2001
  10. Differential survival signaling during angiogenesis
    Alireza Alavi; Fiscal Year: 2004

Detail Information

Publications233 found, 100 shown here

  1. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
    ..As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma...
  2. ncbi The RAF proteins take centre stage
    Claudia Wellbrock
    Signal Transduction Team, Cancer Research UK Centre of Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nat Rev Mol Cell Biol 5:875-85. 2004
    ....
  3. pmc Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions
    W Kolch
    The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, U K
    Biochem J 351:289-305. 2000
    ....
  4. ncbi C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB
    Sonja I Gringhuis
    Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
    Immunity 26:605-16. 2007
    ..Thus, this pathway is involved in regulation of adaptive immunity by DCs to bacterial, fungal, and viral pathogens...
  5. pmc Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma
    Clara Montagut
    Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, USA
    Cancer Res 68:4853-61. 2008
    ..Geldanamycin effectively promotes the degradation of CRAF, thereby revealing a potential therapeutic strategy to overcome resistance to RAF inhibition in a subset of BRAF mutant tumors...
  6. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
    ..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...
  7. ncbi BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis
    Scott M Wilhelm
    Bayer Pharmaceuticals Corporation, West Haven, Connecticut 06516, USA
    Cancer Res 64:7099-109. 2004
    ..These data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis...
  8. pmc B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts
    Catrin A Pritchard
    Department of Biochemistry, University of Leicester, United Kingdom
    Mol Cell Biol 24:5937-52. 2004
    ..They suggest that B-Raf is involved in invasiveness by regulating the proper assembly of actin stress fibers and contractility through a ROCKII/LIMK/cofilin signaling pathway...
  9. ncbi Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes
    Aki Fujioka
    Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita Shi, Osaka 565 0871, Japan
    J Biol Chem 281:8917-26. 2006
    ..This prediction was confirmed experimentally by decreasing the level of Raf using the small interfering RNA technique. This observation verified the usefulness of the parameters collected in this study...
  10. ncbi Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP
    K Yeung
    Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Richmond 02912, USA
    Nature 401:173-7. 1999
    ..RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module...
  11. ncbi Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1
    Eric O'Neill
    The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
    Science 306:2267-70. 2004
    ..Conversely, depletion of Raf-1 from Raf-1+/+ mouse or human cells led to MST2 activation and apoptosis. The concomitant depletion of both Raf-1 and MST2 prevented apoptosis...
  12. ncbi Mechanisms of regulating the Raf kinase family
    Huira Chong
    Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
    Cell Signal 15:463-9. 2003
    ..From studies using mammalian isoforms of Raf, as well as C. elegans lin45-Raf, common patterns and unique differences of regulation have emerged. This review will summarize recent findings on the regulation of Raf kinase...
  13. ncbi Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization
    Mathew J Garnett
    Signal Transduction Team, The Institute of Cancer Research, Cancer Research UK Centre of Cell and Molecular Biology, London
    Mol Cell 20:963-9. 2005
    ..Thus, we have identified a B-RAF-C-RAF-MEK-ERK cascade that signals not only in cancer but also in normal cells...
  14. pmc Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1
    D R Alessi
    Department of Biochemistry, University of Dundee, Scotland
    EMBO J 13:1610-9. 1994
    ....
  15. ncbi Untying the regulation of the Raf-1 kinase
    Amardeep S Dhillon
    The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories Garscube Estate, Glasgow, UK
    Arch Biochem Biophys 404:3-9. 2002
    ..KSR is a dynamic scaffold whose function and localization is regulated by phosphorylation...
  16. pmc Raf-1 regulates Rho signaling and cell migration
    Karin Ehrenreiter
    Department of Microbiology and Genetics, Max F Perutz Laboratories, University Departments at the Vienna Biocenter, 1030 Vienna, Austria
    J Cell Biol 168:955-64. 2005
    ..Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration...
  17. pmc Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism
    J Chen
    Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 98:7783-8. 2001
    ..Thus, Raf-1 may promote cell survival through its protein-protein interactions in addition to its established MEK kinase function...
  18. ncbi Identification of the major phosphorylation sites of the Raf-1 kinase
    D K Morrison
    ABL Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Maryland 21702
    J Biol Chem 268:17309-16. 1993
    ..Interestingly, these RSXSXP sequences are completely conserved throughout evolution in all Raf family members...
  19. ncbi Dephosphorylation of Ser-259 regulates Raf-1 membrane association
    Markus Kubicek
    Department of Cell Biology and Microbiology, Institute of Microbiology and Genetics, Vienna Biocenter, Dr Bohr Gasse 9, 1030 Vienna, Austria
    J Biol Chem 277:7913-9. 2002
    ....
  20. ncbi Active Ras induces heterodimerization of cRaf and BRaf
    C K Weber
    Abteilung für Naturheilkunde und Klinische Pharmakologie and Abteilung Innere Medizin I, Universitat Ulm, D 89081 Ulm, Germany
    Cancer Res 61:3595-8. 2001
    ....
  21. ncbi Modulation of the Ras/Raf/MEK/ERK pathway by Ca(2+), and calmodulin
    Neus Agell
    Departament de Biologia Cel lular i Anatomia Patològica, Institut d Investigacions Biomediques August Pi i Sunyer, Facultat de Medicina Universitat de Barcelona, c Casanova, 143, 08036 Barcelona, Spain
    Cell Signal 14:649-54. 2002
    ..In fibroblasts, CaM binding to EGF receptor and K-Ras(B) may be involved in the downregulation of the pathway after its activation, allowing a proliferative signalling...
  22. ncbi Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention
    F Chang
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 17:1263-93. 2003
    ..The prospects of targeting this pathway for therapeutic intervention in leukemia and other cancers will be evaluated...
  23. ncbi Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein
    Kevin C Corbit
    Department of Neurobiology, Pharmacology and Physiology, and Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 278:13061-8. 2003
    ..Taken together, these results constitute the first model showing how phosphorylation by PKC relieves a key inhibitor of the Raf/MAP kinase signaling cascade and may represent a general mechanism for the regulation of MAP kinase pathways...
  24. pmc Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation
    C S Mason
    CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB
    EMBO J 18:2137-48. 1999
    ..Thus, there are considerable differences between the activation of the Raf proteins; Ras-GTP mediates two phosphorylation events required for Raf-1 activation but does not regulate such events for B-Raf...
  25. pmc Raf-1 sets the threshold of Fas sensitivity by modulating Rok-alpha signaling
    Daniela Piazzolla
    Max F Perutz Laboratories, Department of Microbiology and Immunobiology, Campus Vienna Biocenter, 1030 Vienna, Austria
    J Cell Biol 171:1013-22. 2005
    ..Thus, Raf-1 has an essential function in regulating Fas expression and setting the threshold of Fas sensitivity during embryonic life...
  26. ncbi Mitogen-activated protein kinase pathways
    M J Robinson
    University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 904, 1 USA
    Curr Opin Cell Biol 9:180-6. 1997
    ....
  27. pmc Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein
    K Yeung
    Department of Molecular Biology, Brown University, Providence, Rhode Island 02912, USA
    Mol Cell Biol 20:3079-85. 2000
    ..The properties of RKIP reveal the specific sequestration of interacting components as a novel motif in the cell's repertoire for the regulation of signaling pathways...
  28. ncbi Raf-1 activates MAP kinase-kinase
    J M Kyriakis
    Diabetes Unit, Medical Services, Massachusetts General Hospital, Charlestown 02129
    Nature 358:417-21. 1992
    ..These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified...
  29. ncbi Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade
    J Avruch
    Diabetes Unit and Medical Services, Massachusetts General Hospital, Boston 02114, USA
    Recent Prog Horm Res 56:127-55. 2001
    ..We will then review in more detail current understanding of the biochemical mechanism through which the Ras proto-oncogene, in collaboration with the 14-3-3 protein and other protein kinases, initiates activation of the Raf kinase...
  30. ncbi Ras signalling on the endoplasmic reticulum and the Golgi
    Vi K Chiu
    Department of Medicine, Cell Biology and Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Nat Cell Biol 4:343-50. 2002
    ..Thus, Ras signalling is not limited to the PM, but also proceeds on the endomembrane...
  31. ncbi cAMP-dependent protein kinase and Ca2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation of extracellular regulated kinase in response to glucagon-like peptide-1 in pancreatic beta-cells
    Edith Gomez
    Department of Biochemistry, University of Leicester, United Kingdom
    J Biol Chem 277:48146-51. 2002
    ..This requires 1) the activation of cAMP-dependent protein kinase, 2) an influx of extracellular Ca(2+) through L-type voltage-gated calcium channels, and 3) the activation of CaM kinase II...
  32. ncbi Raf-1 addiction in Ras-induced skin carcinogenesis
    Karin Ehrenreiter
    Max F Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria
    Cancer Cell 16:149-60. 2009
    ..These data link the Raf-1:Rok-alpha complex to STAT3/Myc activation and delineate a pathway crucial for cell fate decision in Ras-induced tumorigenesis...
  33. ncbi The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanism
    Paul C Chin
    Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083, USA
    J Neurochem 90:595-608. 2004
    ....
  34. ncbi The complexity of Raf-1 regulation
    D K Morrison
    Molecular Basis of Carcinogenesis Laboratory, ABL Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA
    Curr Opin Cell Biol 9:174-9. 1997
    ..The picture clearly emerging is that Raf-1 activity can be regulated by multiple mechanisms...
  35. ncbi Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis
    Pavel Krejci
    Medical Genetics Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
    J Cell Sci 118:5089-100. 2005
    ..We conclude that CNP utilizes both direct and indirect ways to counteract the effects of FGF signaling in a chondrocyte environment...
  36. ncbi Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis
    Anton Yuryev
    Novartis Institute for Biomedical Research, Summit, NJ 07901, USA
    Genomics 81:112-25. 2003
    ..We propose possible functional consequences of these novel Raf interactions...
  37. ncbi The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways
    T Kataoka
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Epalinges, CH 1066, Switzerland
    Curr Biol 10:640-8. 2000
    ..We investigated the level at which the two conflicting Fas signals diverge and the protein(s) that are implicated in switching the response...
  38. ncbi Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis
    Zheng Fu
    Program in Immunology, School of Medicine, University of Michigan, Ann Arbor 48109 0940, USA
    J Natl Cancer Inst 95:878-89. 2003
    ..We examined whether RKIP functions as a suppressor of metastasis...
  39. ncbi Microtubule integrity regulates Pak leading to Ras-independent activation of Raf-1. insights into mechanisms of Raf-1 activation
    M Zang
    Diabetes and Metabolism Research Unit, Endocrinology Section, Evans Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    J Biol Chem 276:25157-65. 2001
    ....
  40. ncbi Potential contributory role of H-Ras, a small G-protein, in the development of retinopathy in diabetic rats
    Renu A Kowluru
    Kresge Eye Institute, Wayne State University, Detroit, Michigan, USA
    Diabetes 53:775-83. 2004
    ..Thus, the results suggest that functional activation of H-Ras might be one of the signaling steps involved in glucose-induced capillary cell apoptosis and supports the role of H-Ras in the development of retinopathy in diabetes...
  41. pmc Regulation and role of Raf-1/B-Raf heterodimerization
    Linda K Rushworth
    Signalling and Proteomics Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Glasgow G61 1BD, United Kingdom
    Mol Cell Biol 26:2262-72. 2006
    ....
  42. pmc Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation
    S Wang
    Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Mol Cell Biol 18:7487-98. 1998
    ....
  43. pmc A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function
    A D Catling
    Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville 22908, USA
    Mol Cell Biol 15:5214-25. 1995
    ..These observations indicate a critical role for the PR sequence in directing specific protein-protein interactions important for the activation, inactivation, and downstream functioning of the MEKs...
  44. ncbi Localization of endogenous Grb10 to the mitochondria and its interaction with the mitochondrial-associated Raf-1 pool
    A Nantel
    Eukaryotic Genetics Group, Biotechnology Research Institute, National Research Council, Department of Anatomy, Montreal, H4P 2R2 Quebec, Canada
    J Biol Chem 274:35719-24. 1999
    ..Thus, we infer that Grb10 may regulate signaling between plasma membrane receptors and the apoptosis-inducing machinery on the mitochondrial outer membrane by modulating the anti-apoptotic activity of mitochondrial Raf-1...
  45. ncbi Mammalian Ras interacts directly with the serine/threonine kinase Raf
    A B Vojtek
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98104
    Cell 74:205-14. 1993
    ..Using purified bacterially expressed fusion proteins, we show, furthermore, that Ras and the N-terminal region of Raf associate directly in vitro and that this interaction is dependent on GTP bound to Ras...
  46. pmc Inducible gene deletion reveals different roles for B-Raf and Raf-1 in B-cell antigen receptor signalling
    Tilman Brummer
    Department of Molecular Immunology, Biology III, University of Freiburg and Max Planck Institute for Immunobiology, Stuebeweg 51, Germany
    EMBO J 21:5611-22. 2002
    ..Our study shows that BCR-mediated ERK activation involves a cooperation of both B-Raf and Raf-1, which are activated specifically in a temporally distinct manner...
  47. ncbi Raf and akt mediate distinct aspects of sensory axon growth
    Annette Markus
    Neuroscience Center, University of North Carolina, 103 Mason Farm Road, Chapel Hill 27599, USA
    Neuron 35:65-76. 2002
    ..Activated Raf-1 caused axon lengthening comparable to NGF, while active Akt increased axon caliber and branching. Our results suggest that the different Trk effector pathways mediate distinct morphological aspects of developing neurons...
  48. ncbi ERK signalling and oncogene transformation are not impaired in cells lacking A-Raf
    Kathryn Mercer
    Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK
    Oncogene 21:347-55. 2002
    ..Interestingly, B-Raf and Raf-1 activity towards MEK as measured by the immunoprecipitation kinase cascade assay are both significantly increased in the A-Raf deficient MEFs...
  49. ncbi 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...
  50. ncbi Anti-apoptotic signaling of the insulin-like growth factor-I receptor through mitochondrial translocation of c-Raf and Nedd4
    F Peruzzi
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 276:25990-6. 2001
    ..This failure is accompanied by a loss of cytochrome c from the mitochondria. The 14.3.3/Raf-1/Nedd4 pathway is operative in the presence or absence of the insulin receptor substrate-1...
  51. ncbi Bcl-2 proteins: master switches at the intersection of death signaling and the survival control by Raf kinases
    Ulf R Rapp
    Institut für Medizinische Strahlenkunde und Zellforschung MSZ, Universitat Wurzburg, Versbacher Str 5, 97078 Wurzburg, Germany
    Biochim Biophys Acta 1644:149-58. 2004
    ..Within the scope of this review, we will discuss the contribution of Bcl-2-dependent signaling pathways to cell survival by Raf kinases and also address the underlying mechanisms...
  52. pmc Protective role of Raf-1 in Salmonella-induced macrophage apoptosis
    V Jesenberger
    Department of Cell and Microbiology, Institute of Microbiology and Genetics, Vienna Biocenter, Austria
    J Exp Med 193:353-64. 2001
    ..Instead, pathogen-mediated activation of caspase-1 is enhanced selectively, implying that Raf-1 antagonizes stimulus-induced caspase-1 activation and apoptosis...
  53. ncbi Raf meets Ras: completing the framework of a signal transduction pathway
    J Avruch
    Diabetes Unit, Massachusetts General Hospital, Boston
    Trends Biochem Sci 19:279-83. 1994
    ....
  54. pmc A Raf-1 mutant that dissociates MEK/extracellular signal-regulated kinase activation from malignant transformation and differentiation but not proliferation
    Amardeep S Dhillon
    The Beatson Institute for Cancer Research, CR UK Beatson Laboratories, Garscube Estate, Bearsden, Glasgow G61 1BD, Scotland, UK
    Mol Cell Biol 23:1983-93. 2003
    ..The results further suggest that RafS259 mutants inhibit signaling pathways required to promote these biological processes...
  55. ncbi The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling
    A Bergmann
    Massachusetts Institute of Technology, Howard Hughes Medical Institute, Department of Biology, Cambridge 02139, USA
    Cell 95:331-41. 1998
    ..These findings define a novel mechanism by which growth factor signaling directly inactivates a critical component of the intrinsic cell death machinery. These studies provide further insights into the function of ras as an oncogene...
  56. ncbi Hyperactive Ras in developmental disorders and cancer
    Suzanne Schubbert
    Department of Pediatrics, University of California, 513 Parnassus Avenue, Room HSE 302, San Francisco, California 94143, USA
    Nat Rev Cancer 7:295-308. 2007
    ..Here we will discuss the implications of germline mutations in the Ras-Raf-MEK-ERK pathway for understanding normal developmental processes and cancer pathogenesis...
  57. ncbi Raf kinase activation of adenylyl cyclases: isoform-selective regulation
    Qingming Ding
    Cell Biology Research Group, Robarts Research Institute, 100 Perth Dr, London, ON, Canada N6A 5K8
    Mol Pharmacol 66:921-8. 2004
    ..These functional interactions (as well as the physical association) between adenylyl cyclases and Raf kinases suggest an important but previously unrecognized interaction between these two key regulatory enzymes...
  58. pmc Association of c-Raf expression with survival and its targeting with antisense oligonucleotides in ovarian cancer
    F McPhillips
    ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, EH4 2XU, UK
    Br J Cancer 85:1753-8. 2001
    ..These data indicate that high levels of c-Raf expression may be important in ovarian cancer and use of antisense ODNs targeted to c-Raf could provide a strategy for the treatment of this disease...
  59. 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
    ....
  60. ncbi In melanoma, RAS mutations are accompanied by switching signaling from BRAF to CRAF and disrupted cyclic AMP signaling
    Nicolas Dumaz
    Signal Transduction Team, The Institute for Cancer Research, Cancer Research UK Centre of Cell and Molecular Biology, London, United Kingdom
    Cancer Res 66:9483-91. 2006
    ..These data have important implications for the development of therapeutic strategies to treat this life-threatening disease...
  61. ncbi Bcl-2 targets the protein kinase Raf-1 to mitochondria
    H G Wang
    The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, California 92037, USA
    Cell 87:629-38. 1996
    ..Bcl-2 can therefore target Raf-1 to mitochondrial membranes, allowing this kinase to phosphorylate BAD or possibly other protein substrates involved in apoptosis regulation...
  62. ncbi Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2
    Kristina Lorenz
    Institut fur Pharmakologie und Toxikologie, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    Nature 426:574-9. 2003
    ..A physiological role for this mechanism is shown in cardiomyocytes in which the downregulation of RKIP restrains beta-adrenergic signalling and contractile activity...
  63. pmc Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis
    Osamu Yamaguchi
    Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    J Clin Invest 114:937-43. 2004
    ..The ablation of ASK1 rescued heart dysfunction and dilatation as well as cardiac fibrosis. These results indicate that Raf-1 promotes cardiomyocyte survival through a MEK/ERK-independent mechanism...
  64. ncbi C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1
    J Muller
    Regulation of Cell Growth Laboratory, Center for Cancer Research, NCI Frederick, Frederick, MD 21702, USA
    Mol Cell 8:983-93. 2001
    ....
  65. ncbi Raf proteins and cancer: B-Raf is identified as a mutational target
    Kathryn E Mercer
    Department of Biochemistry, University of Leicester, University Road, LE1 7RH, Leicester, UK
    Biochim Biophys Acta 1653:25-40. 2003
    ....
  66. pmc MEK kinase activity is not necessary for Raf-1 function
    M Huser
    Department of Biochemistry, MRC Toxicology Unit and Division of Biomedical Services, University of Leicester, University Road, Leicester LE1 7RH, UK
    EMBO J 20:1940-51. 2001
    ..These results strongly argue that MEK kinase activity of Raf-1 is not essential for normal mouse development and that Raf-1 plays a key role in preventing apoptosis...
  67. pmc CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations
    K S M Smalley
    The Wistar Institute, Philadelphia, PA, USA
    Oncogene 28:85-94. 2009
    ..In summary, we have identified a group of melanomas with low-activity BRAF mutations that are reliant upon CRAF-mediated survival activity...
  68. ncbi Glucose-dependent insulinotropic polypeptide activates the Raf-Mek1/2-ERK1/2 module via a cyclic AMP/cAMP-dependent protein kinase/Rap1-mediated pathway
    Jan A Ehses
    Department of Physiology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 277:37088-97. 2002
    ..These results establish the importance of GIP in the cellular regulation of the ERK1/2 module and identify a role for cAMP in coupling its G protein-coupled receptors to ERK1/2 activity in pancreatic beta-cells...
  69. ncbi Role of Raf-1 and FAK in cell density-dependent regulation of integrin-dependent activation of MAP kinase
    Lianfeng Zhang
    Division of Tumor Biology, Northeastern Ontario Regional Cancer Center, Sudbury, Ontario P3E 5J1, Canada
    Carcinogenesis 23:1251-8. 2002
    ..These results suggest that the active form of Raf-1 may interrupt cell-cell contact inhibition by promoting alphav integrin expression, which has been implicated in cell aggregation...
  70. ncbi PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway
    Lucy C Coles
    School of Biomedical Sciences, University of Nottingham Medical School, Queen s Medical Centre, Nottingham NG7 2UH, UK
    Oncogene 21:2236-44. 2002
    ..Our findings indicate that PAK1 primes MEK1 for activation by Raf-1 and imply another level of regulation in the ERK cascade...
  71. ncbi Reactive oxygen species mediate cyclic strain-induced endothelin-1 gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in endothelial cells
    T H Cheng
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC
    J Mol Cell Cardiol 33:1805-14. 2001
    ..Our data demonstrate that strain-induced Et-1 gene expression is modulated by ROS via Ras/Raf/ERK signaling pathway, and indicate the responsiveness of the AP-1 binding site for strain-induced Et-1 expression...
  72. pmc p19ARF-independent induction of p53 and cell cycle arrest by Raf in murine keratinocytes
    E Roper
    Imperial Cancer Research Fund, London, UK
    EMBO Rep 2:145-50. 2001
    ..Thus, p19ARF is not essential for Raf-induced p53 induction and cell cycle arrest in keratinocytes, indicating that oncogenes engage p53 activity via multiple mechanisms...
  73. pmc The transcriptional response to Raf activation is almost completely dependent on Mitogen-activated Protein Kinase Kinase activity and shows a major autocrine component
    Almut Schulze
    Gene Expression Analysis, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
    Mol Biol Cell 15:3450-63. 2004
    ..The use of transcriptional profiling in this way allows detailed analysis of the architecture of signaling pathways to be undertaken...
  74. ncbi Raf kinases in lung tumor development
    Ulf R Rapp
    Institut für Medizinische, Strahlenkunde und Zellforschung MSZ, Bayerische Julius Maximilians Universität, Universitat Wurzburg, Versbacher Strasse 5, D 97078, Wurzburg, Germany
    Adv Enzyme Regul 43:183-95. 2003
  75. pmc The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf
    W Li
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 USA
    Genes Dev 14:895-900. 2000
    ..Sur-8 interacts with Ras and Raf and is able to form a ternary complex with the two proteins. Thus, Sur-8 may function as a scaffold that enhances Ras-MAP kinase signal transduction by facilitating the interaction between Ras and Raf...
  76. ncbi Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye
    Lihui Yang
    Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Dev Cell 4:359-69. 2003
    ..Our results suggest that, rather than triggering all or none responses, EGFR coordinates partially independent processes as the eye differentiates...
  77. ncbi The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338
    A J King
    Department of Medicine, Indiana University School of Medicine, The Walther Oncology Center, Indianapolis 46202, USA
    Nature 396:180-3. 1998
    ..As guanine-nucleotide-exchange activity on Rac can be stimulated by a Ras-dependent phosphatidylinositol-3-OH kinase, a mechanism could exist through which one Ras effector pathway can be influenced by another...
  78. ncbi Differential activation mechanisms of Erk-1/2 and p70(S6K) by glucose in pancreatic beta-cells
    Isabelle Briaud
    Pacific Northwest Research Institute, Seattle, Washington, USA
    Diabetes 52:974-83. 2003
    ..In contrast, glucose-induced p70(S6K) activation, in the same beta-cells, was mediated by a distinct signaling pathway independent of Ca(2+)/cAMP, most likely via mTOR-kinase acting as an "ATP-sensor."..
  79. ncbi Role of Raf in vascular protection from distinct apoptotic stimuli
    Alireza Alavi
    Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 301:94-6. 2003
    ..These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis...
  80. ncbi Serum proteomics of lung adenocarcinomas induced by targeted overexpression of c-raf in alveolar epithelium identifies candidate biomarkers
    Bijon Chatterji
    Department of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
    Proteomics 7:3980-91. 2007
    ..Disease association of these proteins in human malignancies has been reported. Thus, an identification of regulated serum proteins in this lung cancer disease model provides excellent opportunities for the search of novel biomarkers...
  81. ncbi Extracellular signal regulated kinase (ERK)/mitogen activated protein kinase (MAPK)-independent functions of Raf kinases
    Alison Hindley
    The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, G61 1BD, UK
    J Cell Sci 115:1575-81. 2002
    ..Other studies have suggested that Raf has kinase-independent functions and may act as a scaffold protein...
  82. ncbi An old kinase on a new path: Raf and apoptosis
    Manuela Baccarini
    Institute of Microbiology and Genetics, Vienna Biocenter, Dr Bohr Gasse 9, 1030 Vienna, Austria
    Cell Death Differ 9:783-5. 2002
  83. pmc Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene
    M Mikula
    Department of Cell and Microbiology, Institute of Microbiology and Genetics and Research Institute of Molecular Pathology, Vienna Biocenter, 1030 Vienna, Austria
    EMBO J 20:1952-62. 2001
    ..These results indicate that the essential function of Raf-1 is to counteract apoptosis rather than to promote proliferation, and that effectors distinct from the MEK/ERK cascade must mediate the anti-apoptotic function of Raf-1...
  84. pmc Apoptosis suppression by Raf-1 and MEK1 requires MEK- and phosphatidylinositol 3-kinase-dependent signals
    A von Gise
    , , , Germany
    Mol Cell Biol 21:2324-36. 2001
    ..Moreover, a constitutively active form of AKT synergizes with Raf-1 in apoptosis suppression. In summary these data strongly suggest a Raf effector pathway for cell survival that is mediated by MEK and AKT...
  85. ncbi Phosphorylation of Raf-1 by p21-activated kinase 1 and Src regulates Raf-1 autoinhibition
    Nancy H Tran
    Department of Integrative Biology and Pharmacology, University of Texas Houston Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 278:11221-6. 2003
    ..These results demonstrate that the autoinhibitory domain of Raf-1 is functional in mammalian cells and that its interaction with the Raf-1 catalytic domain is regulated by phosphorylation of serine 338 and tyrosines 340 and 341...
  86. ncbi Isotype-specific functions of Raf kinases
    C Hagemann
    Institut für Medizinische Strahlenkunde und Zellforschung MSZ, Versbacher Strasse 5, Wurzburg, D 97078, Germany
    Exp Cell Res 253:34-46. 1999
    ..Recently we were able to identify candidates for such Raf-isoform-specific interaction partners...
  87. ncbi Raf-1 protein kinase is required for growth of induced NIH/3T3 cells
    W Kolch
    Laboratory of Viral Carcinogenesis, NIH NCI, Frederick Cancer Research and Development Center, Maryland 21702 1201
    Nature 349:426-8. 1991
    ..We conclude that raf functions as an essential signal transducer downstream of serum growth factor receptors, protein kinase C and ras...
  88. ncbi Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells
    X Wu
    Department of Biological Chemistry and the Institute of Gerontology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 271:3265-71. 1996
    ..Interestingly, A-Raf does not activate MEK2, although c-Raf can activate both MEK1 and MEK2. Our data demonstrated that A-Raf is, indeed, a MEK1 activator and may play a role in growth factor signaling...
  89. ncbi Disruption of tumor cell adhesion promotes angiogenic switch and progression to micrometastasis in RAF-driven murine lung cancer
    Fatih Ceteci
    Institut fur Medizinische Strahlenkunde und Zellforschung, Universitat Wurzburg, Versbacher Strasse 5, 97078, Wurzburg, Germany
    Cancer Cell 12:145-59. 2007
    ..In vivo, lung tumor cells with disrupted E-cadherin expressed beta-catenin target genes normally found in other endodermal lineages suggesting that reprogramming may be involved in metastatic progression...
  90. ncbi Towards a lung adenocarcinoma proteome map: studies with SP-C/c-raf transgenic mice
    Heike Rütters
    Department of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai Fuchs Strasse 1, 30625 Hannover, Germany
    Proteomics 6:3127-37. 2006
    ..This map provides valuable insight into expression of pulmonary proteins associated with lung adenocarcinomas, some of which may be of utility as diagnostic markers in clinical trials...
  91. ncbi A dimerization-dependent mechanism drives RAF catalytic activation
    Thanashan Rajakulendran
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada
    Nature 461:542-5. 2009
    ..Together, our data identify the side-to-side dimer interface of RAF as a potential therapeutic target for intervention in BRAF-dependent tumorigenesis...
  92. ncbi Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors
    Tsuneo Ikenoue
    Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
    Cancer Res 63:8132-7. 2003
    ..These results suggest that the B-Raf activation segment mutations other than V599E reported in colorectal tumors do not necessarily contribute to carcinogenesis by increasing kinase and transforming activities...
  93. ncbi Overexpressed Raf-1 and phosphorylated cyclic adenosine 3'-5'-monophosphatate response element-binding protein are early markers for lung adenocarcinoma
    Maria Cekanova
    Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 37996, USA
    Cancer 109:1164-73. 2007
    ....
  94. ncbi Endothelial apoptosis in Braf-deficient mice
    L Wojnowski
    Section on Genetics, National Institute of Mental Health National Human Genome Research Institute, Bethesda, Maryland 20892, USA
    Nat Genet 16:293-7. 1997
    ..These results establish Braf as a critical signalling factor in the formation of the vascular system and provide the first genetic evidence for an essential role of Raf gene in the regulation of programmed cell death...
  95. ncbi Axin inhibits extracellular signal-regulated kinase pathway by Ras degradation via beta-catenin
    Soung Hoo Jeon
    National Research Laboratory of Molecular Complex Control, and Department of Biotechnology, Yonsei University, Seoul, Korea
    J Biol Chem 282:14482-92. 2007
    ..This study provides evidences for the role of the Ras-ERK pathway in carcinogenesis caused by mutations of the Wnt/beta-catenin pathway components...
  96. pmc Raf-1 antagonizes erythroid differentiation by restraining caspase activation
    Andrea Kolbus
    Research Institute of Molecular Pathology, Institute of Microbiology and Genetics, Vienna Biocenter, 1030 Vienna, Austria
    J Exp Med 196:1347-53. 2002
    ..These results reveal an essential function of Raf-1 in erythropoiesis and demonstrate that the ability of Raf-1 to restrict caspase activation is biologically relevant in a context distinct from apoptosis...
  97. ncbi Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma development in severe combined immunodeficient mice
    Barbara Bedogni
    Division of Radiation and Cancer Biology, Stanford University, Stanford, California, USA
    Cancer Res 64:2552-60. 2004
    ..These studies demonstrate that topical treatment targeting Ras effectors is efficacious, without systemic toxicities, and may prove to be useful in treating and preventing the progression of cutaneous melanoma...
  98. pmc Insulin stimulates primary beta-cell proliferation via Raf-1 kinase
    Jennifer L Beith
    Laboratory of Molecular Signalling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Endocrinology 149:2251-60. 2008
    ..These findings have significant implications for the understanding of the regulation of beta-cell mass in both the hyperinsulinemic and insulin-deficient states that occur in the various forms of diabetes...
  99. pmc Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo: CI-1040 strongly reduces growth and improves lung structure
    Boris W Kramer
    Universitäts Kinderklinik Würzburg, D 97080 Wurzburg, Germany
    BMC Cancer 4:24. 2004
    ..In this study the effect of the Raf kinase inhibitor BAY 43-9006 and of the MEK inhibitor CI-1040 (PD184352) on a Raf dependent lung tumor mouse model was analyzed in detail...
  100. ncbi Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1
    Mengwei Zang
    Diabetes and Metabolism Research Unit, Endocrinology Section, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 277:4395-405. 2002
    ..Taken together, the results indicate that the interaction depends on the active conformations of Pak and Raf. They also argue that Pak1 is a physiological candidate for phosphorylation of Raf Ser(338) during the course of Raf activation...
  101. pmc Autoregulation of the Raf-1 serine/threonine kinase
    R E Cutler
    Molecular Basis of Carcinogenesis Laboratory, Advanced BioSciences Laboratories Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 95:9214-9. 1998
    ....

Research Grants62

  1. REGULATION OF THE SENSITIVITY OF DOPAMINE RECEPTORS
    KIM ARTHUR NEVE; Fiscal Year: 2013
    ..Analysis of wild type and mutant dopamine receptors expressed in mammalian cell lines, in neurons, and in vivo offers powerful model systems with which to perform basic research with important clinical implications. ..
  2. Neurochemical Basis of Opiate Addiction
    HORACE LOH; Fiscal Year: 2013
    ..Our proposed studies will link the action of the various protein kinases recruited and activated by OPRM1 in the behavioral responses to the chronic drug treatment. ..
  3. INTERACTIONS OF MYOTONIC DYSTROPHY PROTEIN KINASE
    Henry Epstein; Fiscal Year: 2004
    ..These results would clearly provide a foundation for better understanding of the role that DMPK may play in the pathogenesis of DM1 and for a potentially rational design of therapeutics. ..
  4. Protein inhibitor of Raf-1 kinase
    Kam Yeung; Fiscal Year: 2005
    ..In summary, I believe that the experiments in this proposal will provide a new handle for understanding Raf- 1 signaling, and will initiate studies to expose the full spectrum of RKIP functions. ..
  5. RAS CAAX PEPTIDOMIMETICS IN PULMONARY INFLAMMATION
    Jonathan Finder; Fiscal Year: 2000
    ..The adjacent laboratories of Drs. Sebti, Davies and Pitt are extremely favorable for this project because of their work in the investigation of small G proteins, signal transduction, gene transfer, and pulmonary vascular physiology. ..
  6. ROLE OF RAF IN RAS TRANSFORMATION
    Sharon Campbell; Fiscal Year: 2000
    ..4) To investigate the functional role of phosphatidylserine and Ras in the regulation of Raf kinase activity. ..
  7. ETHANOL, NEURAL DIFFERENTIATION, AND PROTEIN KINASE C
    Robert Messing; Fiscal Year: 1999
    ..In addition, these studies will identify and test PKC isozyme-selective agents that may eventually prove useful as drugs in the treatment of ethanol neurotoxicity. ..
  8. KINASE ENCODING PROTO-ONCOGENES IN IL-2 SIGNAL TRANSDUCT
    John Reed; Fiscal Year: 1993
    ....
  9. CHEMOKINE RECEPTORS AND HIV MEDIATED SIGNALING
    Waldemar Popik; Fiscal Year: 2001
    ..They believe that this study will contribute to our better understanding of HIV-1-induced pathogenicity and will provide a rational basis for new approaches to inhibit HIV replication. ..
  10. Differential survival signaling during angiogenesis
    Alireza Alavi; Fiscal Year: 2004
    ..abstract_text> ..
  11. LPS INTERACTIONS WITH BRAIN ENDOTHELIAL CELLS
    Moshe Arditi; Fiscal Year: 2000
    ....
  12. Role of Src in the endothelial response to VEGF
    Jeffrey Lindquist; Fiscal Year: 2006
    ....
  13. Combination Strategies for Angiogenesis Inhibition
    Keith Flaherty; Fiscal Year: 2008
    ..He is a recognized leader in the field of investigational therapies, has a record of mentoring successful clinical researchers, and is committed to Dr. Flaherty's training. ..
  14. VEGF and bone remodeling in skeletal metastases
    Evan Keller; Fiscal Year: 2005
    ..In this aim, we will test which VEGF isoform contributes to CaP cells' osteoblastic activity. We will also evaluate if VEGF induces this activity through MAPK. ..
  15. Genetics of Longevity and Age-Sensitive Traits in Mice
    Richard Miller; Fiscal Year: 2008
    ..abstract_text> ..
  16. DEVELOPMENT OF MATURE ZEBRAFISH AS AN ANIMAL MODEL
    Evan Keller; Fiscal Year: 2006
    ....
  17. WILD DERIVED MOUSE STOCKS--NEW MODELS FOR AGING RESEARCH
    Richard Miller; Fiscal Year: 2004
    ....
  18. Role of EGFR in Viral Infected Lung Epithelial Cells
    Martha M Monick; Fiscal Year: 2010
    ..Completion of these studies will add to our understanding of mechanisms of RSV infection of airway epithelium and the role of targeted signaling pathways in the subsequent inflammation and life span of infected cells. ..
  19. Prostate Cancer Metastasis Suppressor: Role of RKIP
    Evan Keller; Fiscal Year: 2008
    ..when completed, we hope this work will lead to a better understanding of the mechanisms through which RKIP suppresses metastasis and hopefully identify specific targets to inhibit metastasis. [unreadable] [unreadable]..
  20. AGING, GENE EXPRESSION AND OXIDATIVE STRESS
    Evan Keller; Fiscal Year: 2002
    ....
  21. ssDNA Expression of Triplex-Forming Oligonucleotides
    Yin Chen; Fiscal Year: 2002
    ..Furthermore, it would provide the basis for Phase II work to develop ssDNA generating vectors as potential gene targeting and gene therapy reagents for clinically relevant genes. ..
  22. GENETICS OF AGE SENSITIVE TRAITS IN MICE
    Richard Miller; Fiscal Year: 2003
    ..At best, the program may permit the localization of loci that influence multiple age-sensitive domains and are thus plausible candidates for genes that regulate the rate of aging per se. ..
  23. ETHANOL MEDIATED OSTEOPOROSIS AND INTERLEUKIN 6
    Evan Keller; Fiscal Year: 2002
    ....
  24. PEI Aerosol Delivery of ssDNA Expression Vector
    Yin Chen; Fiscal Year: 2004
    ..The success of this work may lead to a new tool for gene down regulation in vivo and may eventually provide a new approach for the treatment of metastatic tumor. ..
  25. Phase II Clinical Trial Utilizing Lithium for Patients with Neuroendocrine Tumors
    Herbert Chen; Fiscal Year: 2008
    ..Besides surgery, there are limited curative and palliative treatments available to patients with metastatic NE tumors, emphasizing the need for development of other forms of therapy. [unreadable] [unreadable] [unreadable]..
  26. Radiosensitization with the HIV protease inhibior Nelfinavir in NSCLC
    Anjali Gupta; Fiscal Year: 2008
    ..Specific Aim 3. To investigate in vitro the molecular mechanisms by which NFV results in sensitization. [unreadable] [unreadable] [unreadable]..
  27. Two-photon excited fluorescence imaging of placental vasculature in vivo
    Mark Roberson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  28. Phase I/II Study of MS-275 and 5-Azacytidine in Patients with Advanced Non-Small
    CHARLES RUDIN; Fiscal Year: 2008
    ..If successful, this approach could alter the poor prognosis of individuals with this disease. [unreadable] [unreadable] [unreadable]..
  29. Molecular Specialization of Tumor Lymphatics
    Erkki Ruoslahti; Fiscal Year: 2008
    ..Promising compounds emerging from these experiments will be tested in pre-clinical cancer models for treatment of cancer and prevention of metastasis. [unreadable] [unreadable]..
  30. Validating microRNA Analysis in Human Postmortem Brain
    Yogesh Dwivedi; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  31. High Throughput Analysis of Malarial Surface Antigens
    ANDREW OLEINIKOV; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  32. Targeting KSR to Treat Pancreatic Cancer
    Richard N Kolesnick; Fiscal Year: 2010
    ....
  33. Regulation of Mitochondrial Fission/Fusion by PP2A and PKA in Neurons
    Stefan Strack; Fiscal Year: 2009
    ..Our studies may ultimately lead to better therapies for stroke and neurodegenerative disorders. ..
  34. Role of Downstream Signaling in EGFR/HER2 Inhibitor Radiosentitization
    JANIEL SHIELDS; Fiscal Year: 2009
    ....
  35. Regulating Neuroendocrine Phenotype in Cancer
    Herbert Chen; Fiscal Year: 2010
    ..Furthermore, these finding may permit development of components of raf-1 pathway as therapeutic targets in the treatment and palliation of NE tumors. ..
  36. Protein Prenyltransferases in Glucose-Stimulated Insulin Secretion
    Anjaneyulu Kowluru; Fiscal Year: 2010
    ....
  37. MAP Kinase and AKT Signaling in Congestive Heart Failure
    ANTHONY MUSLIN; Fiscal Year: 2009
    ..Our findings will help to identify specific signaling mechanisms involved in the regulation of cardiac myocyte growth and metabolism. ..
  38. MODULATION OF CERAMIDE INDUCED APOPTOSIS IN VIVO
    Richard Kolesnick; Fiscal Year: 2009
    ..If results indicate that overexpressing ASMase effectively radiosensitizes tumor microvasculature, applicability to human tumor radiotherapy will be examined directly using human versions of lentiviral asmase vectors. ..
  39. Regulatory subunits of PP2A in neuronal function
    Stefan Strack; Fiscal Year: 2011
    ..These studies are significant in that they advance our understanding of the critical regulatory enzyme PP2A with the ultimate goal of better therapies for several neurodegenerative disorders. ..
  40. Study of GPR30: a novel estrogen receptor linked to breast cancer.
    Edward J Filardo; Fiscal Year: 2010
    ....
  41. RGS PROTEIN FUNCTION IN CARDIAC PHYSIOLOGY
    ANTHONY MUSLIN; Fiscal Year: 2008
    ..These experiments will help define the role of RGS proteins in the pathogenesis of cardiac hypertrophy and contractile dysfunction and may provide important information for the development of novel therapeutic agents. ..
  42. Signal Transduction Mechanisms in Suicide Brain
    Yogesh Dwivedi; Fiscal Year: 2008
    ..abstract_text> ..
  43. RAS/BRAF Melanoma Mutations: Precursors, Risk, Prognosis
    Nancy Thomas; Fiscal Year: 2004
    ..This study is also expected to lead to identification of new chemotherapeutic targets and more efficient testing of inhibitors for NRAS and BRAF signaling, which have recently been developed. ..
  44. Signaling Pathways in Medullary Thyroid Cancer
    Herbert Chen; Fiscal Year: 2004
    ..abstract_text> ..
  45. FLUORESCENCE ACTIVATED CELL SORTER
    Andrew Yen; Fiscal Year: 2004
    ..The instrument requested is a Dako-Cytomation basic MoFlo plus a UV-vis, vis, and HeNe laser to provide independent UV, vis/488, and red excitation. ..
  46. 'Death' and 'MAPK' pathways with myocardial ischemia
    Junichi Sadoshima; Fiscal Year: 2001
    ..Our study will contribute to the understanding of the mechanism of cardiac myocyte apoptosis by hR and may provide clues to prevent myocyte loss and reduced cardiac function after myocardial I/R. ..
  47. ANTILEUKEMIA ACTIVITY OF PERILLYL ALCOHOL
    Steven Clark; Fiscal Year: 2003
    ..abstract_text> ..
  48. BCR KINASE IN PDGF-MED EFFECTS IN VASCULAR SMOOTH MUSCLE
    Jun Ichi Abe; Fiscal Year: 2002
    ..We propose that Bcr is a novel downstream component of PDGF receptor signaling in vascular smooth muscle, and may be a candidate gene responsible for the atherosclerosis and restenosis. ..
  49. TUMOR CELLS IN CIRCULATION
    Erkki Ruoslahti; Fiscal Year: 2001
    ..Finally, the ability to eliminate tumor cells from the circulation by sFN administration may provide additional protection against tumor cell transfer in bone marrow transplantation used to treat cancer and against tumor metastasis. ..
  50. Novel Signaling Targets in GI Neuroendocrine Tumors
    Herbert Chen; Fiscal Year: 2005
    ..The possibility that raf-l-mediated hormone suppression could be induced by a soluble factor would provide a plausible, therapeutic delivery method. ..
  51. Prevention of cardiac cell death by Mst1 inhibitor
    Junichi Sadoshima; Fiscal Year: 2005
    ..abstract_text> ..
  52. Development of Digital SNP Analysis in Cancer Detection
    Ie Ming Shih; Fiscal Year: 2005
    ..Thus, the encouraging results from this study will ensure the detection of AI in plasma a promising cancer research direction for further exploration. ..
  53. Nutritional Regulation of Fetal Liver Development
    PHILIP GRUPPUSO; Fiscal Year: 2008
    ..Furthermore, we anticipate that our findings will relate to diverse areas of liver biology, including the hepatic response to liver injury, hepatic carcinogenesis, and liver stem cell biology. [unreadable] [unreadable]..
  54. Preclin. model for prevention of NSCLC in former smokers
    HILDEGARD SCHULLER; Fiscal Year: 2006
    ....
  55. Control of T Lymphopoiesis and Growth by Mad Genes
    Brian Iritani; Fiscal Year: 2007
    ..abstract_text> ..
  56. Prevention of neointimal thickening by Mst1
    Junichi Sadoshima; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  57. Anti-aging and Stress Resistance by Sir2
    Junichi Sadoshima; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  58. ANGIOGENESIS INHIBITORS: A MECHANISM OF ACTION
    Erkki Ruoslahti; Fiscal Year: 2006
    ..This study may provide important information on the mechanism of action of a class of angiogenesis inhibitors, information that may prove helpful in designing clinical trials for these compounds. [unreadable] [unreadable]..
  59. NNK, Beta-Adrenergic AA Release and Lung Cancer
    HILDEGARD SCHULLER; Fiscal Year: 2005
    ..2. To determine which products of the AA cascade are formed in untreated cells and in response to NNK, which of these products stimulate DNA synthesis, and what downstream effectors are activated by these products. ..
  60. Drug Sensitivity of Calcium Modulators from Brain Tumor
    Jin Ming Yang; Fiscal Year: 2006
    ..Therefore, the overall goal of this proposal is to identify new drugs for the treatment of GBM. ..
  61. TISSUE TARGETING WITH PHAGE LIBRARIES
    Erkki Ruoslahti; Fiscal Year: 2001
    ..Major advances in tumor therapies could be realized with this technology. Valuable information on the distinguishing characteristics of different vascular beds, including those undergoing angiogenesis, is also likely to ensue. ..