ras proteins

Summary

Summary: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.

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 Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
  3. ncbi Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study
    Jean Yves Douillard
    Centre Rene Gauducheau, Nantes, France
    J Clin Oncol 28:4697-705. 2010
  4. ncbi RAS is regulated by the let-7 microRNA family
    Steven M Johnson
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520, USA
    Cell 120:635-47. 2005
  5. ncbi Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status
    Eric Van Cutsem
    University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
    J Clin Oncol 29:2011-9. 2011
  6. pmc The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website
    S Bamford
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
    Br J Cancer 91:355-8. 2004
  7. ncbi Targeting RAS signalling pathways in cancer therapy
    Julian Downward
    Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Rev Cancer 3:11-22. 2003
  8. ncbi Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial
    Arnaud D Roth
    Oncosurgery, Geneva UniversityHospital, Geneva, Switzerland
    J Clin Oncol 28:466-74. 2010
  9. ncbi Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer
    Carsten Bokemeyer
    University Hospital, Hamburg Eppendorf, Hamburg Eppendorf, Germany
    J Clin Oncol 27:663-71. 2009
  10. pmc A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk
    Lena J Chin
    Department of Molecular, Yale University, New Haven, Connecticut 06520, USA
    Cancer Res 68:8535-40. 2008

Detail Information

Publications290 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 Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
    ..Negation of ras-induced senescence may be relevant during multistep tumorigenesis...
  3. ncbi Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study
    Jean Yves Douillard
    Centre Rene Gauducheau, Nantes, France
    J Clin Oncol 28:4697-705. 2010
    ....
  4. ncbi RAS is regulated by the let-7 microRNA family
    Steven M Johnson
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520, USA
    Cell 120:635-47. 2005
    ..let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer...
  5. ncbi Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status
    Eric Van Cutsem
    University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
    J Clin Oncol 29:2011-9. 2011
    ..An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken...
  6. pmc The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website
    S Bamford
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
    Br J Cancer 91:355-8. 2004
    ..Through the web pages, these data can be queried, displayed as figures or tables and exported in a number of formats. COSMIC is an ongoing project that will continue to curate somatic mutation data and release it through the website...
  7. ncbi Targeting RAS signalling pathways in cancer therapy
    Julian Downward
    Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Rev Cancer 3:11-22. 2003
    The RAS proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation...
  8. ncbi Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial
    Arnaud D Roth
    Oncosurgery, Geneva UniversityHospital, Geneva, Switzerland
    J Clin Oncol 28:466-74. 2010
    ..We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting...
  9. ncbi Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer
    Carsten Bokemeyer
    University Hospital, Hamburg Eppendorf, Hamburg Eppendorf, Germany
    J Clin Oncol 27:663-71. 2009
    ..The influence of KRAS mutation status was investigated...
  10. pmc A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk
    Lena J Chin
    Department of Molecular, Yale University, New Haven, Connecticut 06520, USA
    Cancer Res 68:8535-40. 2008
    ..The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility...
  11. pmc Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF
    Sonja J Heidorn
    The Institute of Cancer Research, Signal Transduction Team, Section of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK
    Cell 140:209-21. 2010
    ....
  12. ncbi The Ras superfamily at a glance
    Krister Wennerberg
    Cytoskeleton Inc, 1830 S Acoma Street, Denver, CO 80223, USA
    J Cell Sci 118:843-6. 2005
  13. ncbi American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy
    Carmen J Allegra
    Division of Hematology Oncology, Department of Medicine, University of Florida Shands CancerCenter, Gainesville, FL, USA
    J Clin Oncol 27:2091-6. 2009
    ....
  14. ncbi Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer
    Rafael G Amado
    Amgen, Inc, One Amgen Center Dr, MS 38 2 B, Thousand Oaks, CA 91320 1799, USA
    J Clin Oncol 26:1626-34. 2008
    ..Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials...
  15. ncbi RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
    Georgia Hatzivassiliou
    Genentech, South San Francisco, California 94080, USA
    Nature 464:431-5. 2010
    ..Furthermore, this work provides new insights into the therapeutic use of ATP-competitive RAF inhibitors...
  16. ncbi Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer
    Marc Peeters
    University Hospital Ghent, Ghent, Belgium
    J Clin Oncol 28:4706-13. 2010
    ..This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status...
  17. ncbi KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer
    Wendy De Roock
    Centre for Human Genetics, Catholic University of Leuven, Leuven, Belgium
    Lancet Oncol 12:594-603. 2011
    ..We review the role of mutations in genes other than KRAS on the efficacy of anti-EGFR therapy, and discuss strategies to target these oncogenic alterations alone or in combination with receptor tyrosine-kinase inhibition...
  18. pmc Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial
    Timothy S Maughan
    School of Medicine, Cardiff University, Cardiff, UK
    Lancet 377:2103-14. 2011
    ....
  19. pmc Ras oncogenes: split personalities
    Antoine E Karnoub
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Rev Mol Cell Biol 9:517-31. 2008
    Extensive research on the Ras proteins and their functions in cell physiology over the past 30 years has led to numerous insights that have revealed the involvement of Ras not only in tumorigenesis but also in many developmental disorders...
  20. ncbi Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab
    Wendy De Roock
    Center for Human Genetics, University of Leuven, Leuven, Belgium
    JAMA 304:1812-20. 2010
    ..Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab...
  21. pmc Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus
    Federica Di Nicolantonio
    Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, IRCC, University of Turin Medical School, Turin, Italy
    J Clin Invest 120:2858-66. 2010
    ..Thus, our results demonstrate that alterations in the KRAS and PIK3CA genes may represent biomarkers to optimize treatment of patients with mTOR inhibitors...
  22. pmc Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum
    Mai Yamauchi
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
    Gut 61:847-54. 2012
    ..Considering a possible role of bowel contents (including microbiome) in carcinogenesis, this study hypothesised that tumour molecular features might gradually change along bowel subsites, rather than change abruptly at splenic flexure...
  23. pmc A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene
    Ji Luo
    Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cell 137:835-48. 2009
    ..Our results suggest a previously underappreciated role for Ras in mitotic progression and demonstrate a pharmacologically tractable pathway for the potential treatment of cancers harboring Ras mutations...
  24. ncbi The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, 44139 Dortmund, Germany
    Science 277:333-8. 1997
    ..Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state...
  25. ncbi Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study
    Kjell Magne Tveit
    Department of Oncology, Oslo University Hospital, 0407 Oslo, Norway
    J Clin Oncol 30:1755-62. 2012
    ..The influence of KRAS mutation status on treatment outcome was also investigated...
  26. ncbi Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer
    Pierre Laurent-Puig
    INSERM UMR S775 Molecular Basis of Xenobiotics Response, Paris, France
    J Clin Oncol 27:5924-30. 2009
    ..However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy...
  27. ncbi Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer
    Jolien Tol
    Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    N Engl J Med 360:563-72. 2009
    ..We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer...
  28. pmc New susceptibility locus for coronary artery disease on chromosome 3q22.3
    Jeanette Erdmann
    Medizinische Klinik II, Universitat zu Lubeck, 23538 Lubeck, Germany
    Nat Genet 41:280-2. 2009
    ..We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11)...
  29. ncbi Genetic prognostic and predictive markers in colorectal cancer
    Axel Walther
    Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, SM2 5PT, UK
    Nat Rev Cancer 9:489-99. 2009
    ..In this Review, we attempt to summarize the sometimes confusing findings, and critically assess those markers already in the public domain...
  30. pmc KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer
    F Loupakis
    Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Istituto Toscano Tumori and Department of Oncology, Transplantes and New Technologies in Medicine, University of Pisa, Via Roma 67 56126 Pisa, Italy
    Br J Cancer 101:715-21. 2009
    ..KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. Additional KRAS mutations are described in CRC...
  31. ncbi Role of miR-143 targeting KRAS in colorectal tumorigenesis
    X Chen
    Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
    Oncogene 28:1385-92. 2009
    ..Taken together, the present study provides the first evidences that miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation...
  32. ncbi How Saccharomyces responds to nutrients
    Shadia Zaman
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Annu Rev Genet 42:27-81. 2008
    ....
  33. pmc PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors
    Filip Janku
    Department of Investigational Cancer Therapeutics, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, FC8 2057, Box 0455, Houston, TX 77030, USA
    Mol Cancer Ther 10:558-65. 2011
    ..5% of patients with diverse solid tumors. The response rate was significantly higher for patients with PIK3CA mutations treated with PI3K/AKT/mTOR pathway inhibitors than for those without documented mutations...
  34. pmc Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion
    Ming Wu
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06519, USA
    Nature 463:545-8. 2010
    ..Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers...
  35. ncbi Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer
    Gordon Hutchins
    Leeds Institute of Molecular Medicine, Leeds University, United Kingdom
    J Clin Oncol 29:1261-70. 2011
    ..We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy...
  36. ncbi Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study
    C Bokemeyer
    Department of Oncology, Hematology, BMT With Section Pneumology, University Hospital, Hamburg Eppendorf, Germany
    Ann Oncol 22:1535-46. 2011
    ....
  37. ncbi Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial
    Jean Yves Douillard
    M D Anderson Cancer Center, Thoracic Head and Neck Medical Oncology, Box 432, 1515 Holcombe Blvd, Houston, TX 77401, USA
    J Clin Oncol 28:744-52. 2010
    ....
  38. ncbi Increased detection sensitivity for KRAS mutations enhances the prediction of anti-EGFR monoclonal antibody resistance in metastatic colorectal cancer
    Francesca Molinari
    Institute of Pathology, Locarno, Switzerland
    Clin Cancer Res 17:4901-14. 2011
    ..We evaluated whether highly sensitive methods for KRAS investigation improve the accuracy of predictions of anti-EGFR MoAbs efficacy...
  39. pmc Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability
    R Sears
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Genes Dev 14:2501-14. 2000
    ..These observations thus define a synergistic role for multiple Ras-mediated phosphorylation pathways in the control of Myc protein accumulation during the initial stage of cell proliferation...
  40. ncbi Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer
    Cecily P Vaughn
    ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA
    Genes Chromosomes Cancer 50:307-12. 2011
    ....
  41. ncbi KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial
    Susan D Richman
    Leeds Institute of Molecular Medicine, St James s Institute of Oncology, Cancer Research UK Genomic Services, University of Leeds, Leeds, UK
    J Clin Oncol 27:5931-7. 2009
    ..We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies...
  42. ncbi The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier
    Oliver E Sturm
    Department of Computing Science, University of Glasgow, Glasgow G12 8QQ, UK
    Sci Signal 3:ra90. 2010
    ..These properties determine biological behavior, including activation kinetics and the response to drugs...
  43. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil R Hingorani
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 7:469-83. 2005
    ..These findings have clear implications for understanding mechanisms of disease pathogenesis, and for the development of detection and targeted treatment strategies...
  44. ncbi High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma
    Edna T Kimura
    Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
    Cancer Res 63:1454-7. 2003
    ..Because these signaling proteins function along the same pathway in thyroid cells, this represents a unique paradigm of human tumorigenesis through mutation of three signaling effectors lying in tandem...
  45. ncbi Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer
    Alberto Bardelli
    Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino, Medical School, Str Prov 142 Km 3 95, 10060 Candiolo, Italy
    J Clin Oncol 28:1254-61. 2010
    ..Finally, unresolved questions such as understanding the molecular basis of response as well the mechanisms of secondary resistance are presented as the future fundamental goals in this research field...
  46. pmc Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health
    William H Chappell
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, USA
    Oncotarget 2:135-64. 2011
    ..Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging...
  47. ncbi KRAS mutations in non-small cell lung cancer
    Gregory J Riely
    Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Am Thorac Soc 6:201-5. 2009
    ..In this review, we summarize the initial discovery of RAS mutations in NSCLC, describe work exploring associations with clinical factors and outcomes, and provide an overview of current approaches to targeting KRAS mutant NSCLC...
  48. ncbi Ras proteins: different signals from different locations
    John F Hancock
    Institute for Molecular Bioscience and Department of Molecular and Cellular Pathology, University of Queensland, Brisbane, Australia 4072
    Nat Rev Mol Cell Biol 4:373-84. 2003
    ..Recent studies have shown that Ras proteins interact dynamically with specific microdomains of the plasma membrane as well as with other internal cell ..
  49. pmc Genomic and biological characterization of exon 4 KRAS mutations in human cancer
    Manickam Janakiraman
    Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Cancer Res 70:5901-11. 2010
    Mutations in RAS proteins occur widely in human cancer...
  50. pmc Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer
    Andrea Sartore-Bianchi
    The Falck Division of Medical Oncology, Ospedale Niguarda Ca Granda, Milan, Italy
    PLoS ONE 4:e7287. 2009
    ....
  51. pmc Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter
    Julia B Cordero
    Beatson Institute for Cancer Research, Cancer Research UK, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
    Dev Cell 18:999-1011. 2010
    ..Our evidence suggests that tumors can evolve into malignancy through oncogenic Ras activation and the hijacking of TNF signaling...
  52. ncbi Small GTP-binding proteins
    Y Takai
    Department of Molecular Biology, Osaka University Graduate School of Medicine Faculty of Medicine, Suita, Japan
    Physiol Rev 81:153-208. 2001
    ..Cascades and cross-talks of small G proteins have also been clarified. In this review, functions of small G proteins and their modes of activation and action are described...
  53. pmc The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation
    William E Tidyman
    Department of Pediatrics, Division of Medical Genetics, University of California, San Francisco, CA 94115, USA
    Curr Opin Genet Dev 19:230-6. 2009
    ..Here we review the clinical and underlying molecular basis for each of these syndromes...
  54. ncbi PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer
    Fotios Loupakis
    Department of Oncology, Azienda USL 6, Istituto Toscano Tumori, Livorno, Italy
    J Clin Oncol 27:2622-9. 2009
    ..This retrospective study investigated the role of PTEN loss, AKT phosphorylation, and KRAS mutations on the activity of cetuximab plus irinotecan in patients with metastatic colorectal cancer (mCRC)...
  55. pmc FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy
    Lucie C Kompier
    Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
    PLoS ONE 5:e13821. 2010
    ..Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic procedure than cystoscopy...
  56. pmc Digital signaling and hysteresis characterize ras activation in lymphoid cells
    Jayajit Das
    Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Cell 136:337-51. 2009
    Activation of Ras proteins underlies functional decisions in diverse cell types. Two molecules, RasGRP and SOS, catalyze Ras activation in lymphocytes...
  57. ncbi Small-molecule inhibition of APT1 affects Ras localization and signaling
    Frank J Dekker
    Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany
    Nat Chem Biol 6:449-56. 2010
    ..is a strategy to modulate cellular localization--and thereby unregulated signaling--caused by palmitoylated Ras proteins. We present the knowledge-based development and characterization of a potent inhibitor of acyl protein ..
  58. pmc Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications
    Robert J Kurman
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Int J Gynecol Pathol 27:151-60. 2008
    ..The model does not replace the histopathologic classification but, by drawing attention to the molecular genetic events that play a role in tumor progression, sheds light on new approaches to early detection and treatment...
  59. 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
    ....
  60. ncbi Ubiquitous activation of Ras and Jak/Stat pathways in human HCC
    Diego F Calvisi
    Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4262, USA
    Gastroenterology 130:1117-28. 2006
    ..Here, we define the role for Ras and Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathways in human HCC...
  61. ncbi Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells
    Claudia Scholl
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 137:821-34. 2009
    ....
  62. pmc Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma
    Diego F Calvisi
    Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4262, USA
    J Clin Invest 117:2713-22. 2007
    ....
  63. pmc KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer
    Chen Mao
    Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, People s Republic of China
    PLoS ONE 7:e36653. 2012
    ..To investigate the frequency and relationship of the KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer (CRC)...
  64. pmc TAK1 inhibition promotes apoptosis in KRAS-dependent colon cancers
    Anurag Singh
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
    Cell 148:639-50. 2012
    ..Together, these findings identify TAK1 inhibition as a potential therapeutic strategy for a treatment-refractory subset of colon cancers exhibiting aberrant KRAS and Wnt pathway activation...
  65. pmc Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway
    Oliver A Kent
    Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genes Dev 24:2754-9. 2010
    ..Additionally, KRAS and RREB1 are targets of miR-143/miR-145, revealing a feed-forward mechanism that potentiates Ras signaling...
  66. pmc Cells navigate with a local-excitation, global-inhibition-biased excitable network
    Yuan Xiong
    Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
    Proc Natl Acad Sci U S A 107:17079-86. 2010
    ..Our study brings together heretofore diverse observations on spontaneous cytoskeletal activity, signaling responses to temporal stimuli, and spatial gradient sensing into a unified scheme...
  67. pmc A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
    Albert Lu
    Departament de Biologia Cellular, Immunologia i Neurociencies, Institut d Investigacions Biomediques August Pi i Sunyer, Serveis Cientificotecnics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
    J Cell Biol 184:863-79. 2009
    b>Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis...
  68. pmc A commercial real-time PCR kit provides greater sensitivity than direct sequencing to detect KRAS mutations: a morphology-based approach in colorectal carcinoma
    Barbara Angulo
    Hospital Universitario Madrid Sanchinarro, Laboratorio de Dianas Terapeuticas, Calle Oña 10, Madrid, Spain
    J Mol Diagn 12:292-9. 2010
    ..Sequencing was able to detect KRAS mutations when the mutant DNA represented 10% of the total DNA in 20/74 (27%) of the tumors. When the mutant DNA represented 30% of the total DNA, sequencing could detect mutations in 56/74 (76%)...
  69. ncbi Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab
    Jolien Tol
    Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Eur J Cancer 46:1997-2009. 2010
    ..Here we assess the predictive value of other potential relevant markers involved in the epidermal growth factor receptor (EGFR) signalling pathways for response to cetuximab-based treatment...
  70. pmc Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance
    Nathan T Ihle
    M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Res 69:143-50. 2009
    ....
  71. pmc PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers
    Filip Janku
    Department of Investigational Cancer Therapeutics Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 6:e22769. 2011
    ..Oncogenic mutations of PIK3CA, RAS (KRAS, NRAS), and BRAF have been identified in various malignancies, and activate the PI3K/AKT/mTOR and RAS/RAF/MEK pathways, respectively. Both pathways are critical drivers of tumorigenesis...
  72. ncbi KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer
    Erminia Massarelli
    Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Clin Cancer Res 13:2890-6. 2007
    ..In contrast, KRAS mutation has been shown to predict poor response to such therapy. We tested the utility of combinations of these three markers in predicting response and survival in patients with NSCLC treated with EGFR-TKIs...
  73. pmc Ras conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics
    Barry J Grant
    Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California, United States of America
    PLoS Comput Biol 5:e1000325. 2009
    ....
  74. pmc A multicenter blinded study to evaluate KRAS mutation testing methodologies in the clinical setting
    Vicki Whitehall
    Queensland Institute of Medical Research, Bancroft Building, 300 Herston Road, Herston Queensland 4029, Australia
    J Mol Diagn 11:543-52. 2009
    ..These results demonstrate that a variety of detection methodologies are suitable and provide comparable results for KRAS mutation analysis of clinical samples...
  75. ncbi Regulation of Raf-1 by direct feedback phosphorylation
    Michele K Dougherty
    Laboratory of Protein Dynamics and Signaling, National Cancer Institute Frederick, Frederick, MD 21702, USA
    Mol Cell 17:215-24. 2005
    ..These findings elucidate a critical Raf-1 regulatory mechanism that contributes to the sensitive, temporal modulation of Ras signaling...
  76. ncbi Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells
    Annette S Little
    Laboratory of Molecular Signalling, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK
    Sci Signal 4:ra17. 2011
    ..However, up-regulation of KRAS(13D) leads to activation of multiple KRAS effector pathways, underlining the therapeutic challenge posed by KRAS mutations. These results may have implications for the use of combination therapies...
  77. ncbi Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction
    David Teis
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Dev Cell 3:803-14. 2002
    ..Reduction of MP1 or p14 protein levels by siRNAi results in defective signal transduction. Therefore, our results suggest that the endosomal localization of the p14/MP1-MAPK scaffold complex is crucial for signal transduction...
  78. ncbi miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer
    Shuangni Yu
    Department of Pathology, Peking Union Medical College Hospital, Tsinghua University, Beijing, PR China
    Cancer Res 70:6015-25. 2010
    ..Our findings identify miR-96 as a potent regulator of KRAS, which may provide a novel therapeutic strategy for treatment of pancreatic cancer and other KRAS-driven cancers...
  79. 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...
  80. ncbi The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway
    Marie Dance
    INSERM U563, Département Lipoprotéines et Médiateurs Lipidiques, Site Purpan, Toulouse, France
    Cell Signal 20:453-9. 2008
    ....
  81. ncbi Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer
    Michio Inukai
    Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
    Cancer Res 66:7854-8. 2006
    ....
  82. pmc Ubiquitination of K-Ras enhances activation and facilitates binding to select downstream effectors
    Atsuo T Sasaki
    1Division of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Sci Signal 4:ra13. 2011
    ..Thus, monoubiquitination could enhance GTP loading on K-Ras and increase its affinity for specific downstream effectors, providing a previously unidentified mechanism for Ras activation...
  83. pmc H-Ras nanocluster stability regulates the magnitude of MAPK signal output
    Barak Rotblat
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    PLoS ONE 5:e11991. 2010
    ..Taken together these data demonstrate that the magnitude of the signal output from a GTP-bound H-Ras nanocluster is proportional to its stability...
  84. ncbi Differential modification of Ras proteins by ubiquitination
    Natalia Jura
    Department of Molecular Genetics and Microbiology, Stony Brook University, New York 11794, USA
    Mol Cell 21:679-87. 2006
    b>Ras proteins are essential components of signal transduction pathways that control cell proliferation, differentiation, and survival...
  85. pmc Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing
    Emma Borràs
    Hospital de Terrassa, Ctra, Torrebonica, Terrassa, Spain
    BMC Cancer 11:406. 2011
    ..The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices...
  86. ncbi KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program
    J H J M van Krieken
    Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, 6500, HB, The Netherlands
    Virchows Arch 453:417-31. 2008
    ..We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union...
  87. ncbi Orally administered FTS (salirasib) inhibits human pancreatic tumor growth in nude mice
    Roni Haklai
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel
    Cancer Chemother Pharmacol 61:89-96. 2008
    ....
  88. pmc Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling
    Jamie E Chaft
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA
    Mol Cancer Ther 11:485-91. 2012
    ..Given the high frequency of overlapping mutations, comprehensive genotyping should be carried out on tumor specimens from patients enrolling in clinical trials of PI3K and other targeted therapies...
  89. ncbi Deciphering the deformation modes associated with function retention and specialization in members of the Ras superfamily
    Francesco Raimondi
    Dulbecco Telethon Institute and Department of Chemistry, Via Campi 183, Modena, Italy
    Structure 18:402-14. 2010
    ..Overall, a complete picture of the functional and evolutionary dynamics of the Ras superfamily emerges...
  90. ncbi Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets
    Panagiotis A Konstantinopoulos
    Department of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias, Athens 11527, Greece
    Nat Rev Drug Discov 6:541-55. 2007
    ..Here, we review emerging druggable targets and novel therapeutic approaches targeting prenylation and post-prenylation modifications and the functional regulation of GDP/GTP exchange as exciting alternatives for anticancer therapy...
  91. pmc PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations
    Katsuhiko Nosho
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Neoplasia 10:534-41. 2008
    ..In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level...
  92. ncbi Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab
    Bart Jacobs
    Department of Pathology, Digestive Oncology Unit, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
    J Clin Oncol 27:5068-74. 2009
    ....
  93. ncbi Implications for KRAS status and EGFR-targeted therapies in metastatic CRC
    Nicola Normanno
    Cell Biology and Biotherapy Unit, INT Fondazione Pascale, Naples, Italy
    Nat Rev Clin Oncol 6:519-27. 2009
    ..We summarize the experimental and clinical evidence supporting the use of KRAS testing for the optimal selection of patients with mCRC to be treated with anti-EGFR monoclonal antibodies...
  94. ncbi BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status
    Shi Yang
    Department of Pathology, Boston Medical Center, Boston, MA 02118, USA
    Am J Surg Pathol 28:1452-9. 2004
    ..In contrast, the association of higher levels of CpG island methylation with more advanced histologic changes suggests that CpG island methylation plays a role in serrated polyp progression toward colorectal carcinoma...
  95. pmc Mapping the nucleotide and isoform-dependent structural and dynamical features of Ras proteins
    Alemayehu A Gorfe
    Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California San Diego, La Jolla, CA 92093 0365, USA
    Structure 16:885-96. 2008
    ..We also modeled and simulated N- and K-ras proteins and found that K-ras is more flexible than N- and H-ras...
  96. ncbi A comparison of EGFR and KRAS status in primary lung carcinoma and matched metastases
    Sara E Monaco
    Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA
    Hum Pathol 41:94-102. 2010
    ..Our results suggest that the EGFR and KRAS status of primary lung carcinomas may not predict the status in the corresponding metastases. This observation may have important implications for molecular testing for targeted therapies...
  97. ncbi Blocking oncogenic Ras signaling for cancer therapy
    A A Adjei
    Division of Medical Oncology Mayo Clinic and Foundation, Rochester, MN 55905, USA
    J Natl Cancer Inst 93:1062-74. 2001
    ..Activating mutations in these Ras proteins result in constitutive signaling, thereby stimulating cell proliferation and inhibiting apoptosis...
  98. ncbi The structural basis of the activation of Ras by Sos
    P A Boriack-Sjodin
    Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA
    Nature 394:337-43. 1998
    ..Sos does not impede the binding sites for the base and the ribose of GTP or GDP, so the Ras-Sos complex adopts a structure that allows nucleotide release and rebinding...
  99. pmc Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant
    F Molinari
    Institute of Pathology, Locarno, Switzerland
    Br J Cancer 100:1087-94. 2009
    ....
  100. ncbi High-resolution melting analysis for rapid detection of KRAS, BRAF, and PIK3CA gene mutations in colorectal cancer
    Lisa Simi
    Clinical Biochemistry, Department of Clinical Physiopathology, University of Florence, Florence, Italy
    Am J Clin Pathol 130:247-53. 2008
    ..008), whereas KRAS and BRAF mutations were mutually exclusive (P = .001). This report describes a novel approach for the detection of PIK3CA somatic mutations by HRMA...
  101. ncbi Galectin-1 augments Ras activation and diverts Ras signals to Raf-1 at the expense of phosphoinositide 3-kinase
    Galit Elad-Sfadia
    Department of Neurobiochemistry, The George S Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel
    J Biol Chem 277:37169-75. 2002
    b>Ras proteins activate diverse effector molecules. Depending on the cellular context, Ras activation may have different biological consequences: induction of cell proliferation, senescence, survival, or death...

Research Grants63

  1. Regulation of K-Ras by a Farnesyl-electrostatic Switch
    MARK REID PHILIPS; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Of the three ras genes, kras is most frequently mutated in human cancer. Ras proteins are highly homologous but differ extensively in their C-terminal hypervariable regions that direct post-..
  2. Novel CTD inhibitors with synthetic lethality to oncogenic Ras for cancer therapy
    Bingliang Fang; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The oncogenic Ras proteins play critical roles in the development and maintenance of cancer phenotypes and serve as important targets for anticancer treatment...
  3. FUNCTION OF THE RAS RELATED RAL PROTEINS
    LARRY FEIG; Fiscal Year: 2009
    ..A key property of the Ral signaling cascade is that it is stimulated by Ras proteins. In many studies, including those involving RalGDS knockout mice, suppression of the Ral signaling cascade ..
  4. Function of the Ras Related Ral Protein
    LARRY FEIG; Fiscal Year: 2013
    ..A key property of the Ral signaling cascade is that it is stimulated by Ras proteins. In many studies, including those involving RalGDS knockout mice, the Ral signaling cascade supports Ras-..
  5. The Unfolded Protein Response in Melanoma Progression and Chemoresistance
    Maria S Soengas; Fiscal Year: 2012
    ..We have recently found that tumor-associated BRAF and RAS proteins are opposed by two kinetically, morphologically and mechanistically different anti-proliferative responses...
  6. The Role of RAS/MAPK Signaling in Alveolar Process Development
    Amnon Sharir; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Ras proteins are a family of signal switch molecules that control multiple cellular responses, including proliferation, differentiation, survival and senescence, mostly through activation of the ..
  7. Temporal and Spatial Signaling in Chemotaxis
    Peter N Devreotes; Fiscal Year: 2013
    ..First, tools to measure and control the temporal and spatial activation of Ras proteins, Tor complex 2, and protein kinases B (PKBs) in living cells will be constructed...
  8. Ras Induced Senescence and Tumor Suppression
    Scott W Lowe; Fiscal Year: 2013
    ..This project was inspired by our observation that oncogenic Ras proteins could trigger senescence in primary cells through Rb and p53 dependent mechanisms, thereby preventing malignant ..
  9. Characterization of lcmt in Animal Models of Cancer
    MARK REID PHILIPS; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Ras genes are mutated in cancer more frequently than any other oncogene. Ras proteins associate with membranes by virtue of a series of post-translational modifications that include farnesylation, ..
  10. Intracellular Calcium Signaling
    Tobias Meyer; Fiscal Year: 2013
    ..role of STIM and ER-PM junctions in regulating the transfer of phosphatidylinositol lipids, cholesterol, and Ras proteins between the ER and PM...
  11. Control of Aspergillus fumigatus polarized growth through regulation of Ras prote
    Jarrod Fortwendel; Fiscal Year: 2013
    ..Due to the essential nature of Ras proteins to fungal morphogenesis, the identification and characterization of fungal-specific properties of Ras proteins ..
  12. Ras-Induced Lung Cancer: Key Roles for IKK and NF-kappaB
    ALBERT SIDNEY BALDWIN; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Oncogenic mutations in Ras proteins lead to transforming potential in a number of epithelial cells...
  13. Compartment Specific Signaling of Ras
    MARK REID PHILIPS; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Ras proteins are prototypical GTPases that control signaling pathways by switching between a GDP-bound inactive and a GTP-bound active state...
  14. R-Ras signaling in vascular biology
    Lawrence E Goldfinger; Fiscal Year: 2013
    ..The binding of specific effectors to activated Ras proteins propagates signaling cascades resulting in unique outcomes depending on the Ras family isotype...
  15. Novel Treatment of NF-1 Associated Malignant Peripheral Nerve Sheath Tumors
    Steven L Carroll; Fiscal Year: 2012
    ..NRG-1 promotes the proliferation and/or survival of MPNST cells by activating specific neurofibromin-regulated Ras proteins and their downstream effectors...
  16. Structure and Function of Plasma membrane Nanodomains
    John F Hancock; Fiscal Year: 2012
    ..Caveolae dysfunction has been linked to cell transformation and to muscle disease. Ras proteins operate as molecular switches in many signal transduction pathways and are frequently mutated in human tumors...
  17. Characterizing the role of specific Ras proteins in neurofibroma and MPNST format
    Preeti Tandon; Fiscal Year: 2013
    ..In order to characterize the role of H-Ras, N-Ras and K-Ras proteins in neurofibroma and MPNST development, we hypothesize that specific Ras proteins play distinct roles in ..
  18. Understanding the Role of kB Ras Proteins in Signaling and Development
    Sankar Ghosh; Fiscal Year: 2013
    ..Interestingly, mice lacking (B-Ras proteins also die perinatally due to defects in lung development...
  19. New Mechanisms Regulating Ras and Protein Kinase A Signaling
    Yuqi Wang; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Ras proteins are key molecular switches that transmit signals to control a variety of cellular processes including proliferation, differentiation, and survival...
  20. MECHANISMS OF SIGNAL TRANSDUCTION BY RAS PROTEINS
    Dafna Bar-Sagi; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): It is firmly established that Ras proteins are essential control elements of growth promoting signaling networks...
  21. Regulation of Ras by Monoubiquitination
    Sharon L Campbell; Fiscal Year: 2013
    ..Mutationally activated Ras proteins are refractory to inactivation by GTPase activating proteins, and are persistently GTP- bound, leading to ..
  22. MECHANISMS OF SIGNAL TRANSDUCTION BY RAS PROTEINS
    Dafna Bar Sagi; Fiscal Year: 2009
    ..It is firmly established that Ras proteins are essential control elements of growth promoting signaling networks...
  23. Ras signaling in C. neoformans virulence and development
    Andrew Alspaugh; Fiscal Year: 2012
    ..The studies in this proposal will characterize the ways in which Ras proteins allow microorganisms to respond to the stresses encountered within the infected host...
  24. MECHANISM AND FUNCTION OF PROTEIN PRENYLATION
    Mark D Distefano; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The discovery that Ras proteins are farnesylated and that inhibition of farnesylation prevents cellular transformation has generated an explosion of interest in this post-translational modification;..
  25. The effect of oncogenic Ras signaling strength on cancer
    CHRISTOPHER COUNTER; Fiscal Year: 2013
    ..propose to test this hypothesis in AIM 1 by determining the impact of manipulating the expression of wild-type Ras proteins and the codon bias of KRAS on senescence during early tumorigenesis...
  26. PHEOCHROMOCYTOMAS FROM NEUROFIBROMATOSIS KNOCKOUT MICE
    Arthur Tischler; Fiscal Year: 2003
    ..Neurofibromin is a GTPase-activating protein that can regulate the activity of ras proteins in intracellular signalling...
  27. Identification of Drug Targets for NF1
    Yolanda Sanchez; Fiscal Year: 2010
    ..Therefore, better treatments are needed for NF1 disease. Nf1 is a GTPase-activating protein (GAP) for Ras proteins and loss of NF1 results in increased levels of Ras-GTP, the activated form of Ras, which can lead to many of ..
  28. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID CLAPP; Fiscal Year: 2001
    ..Mammalian GTPase activating proteins (GAPs) regulate Ras proteins by accelerating GTP hydrolysis...
  29. K-Ras4A Trafficking and Signaling
    FREDERICK DEECHEN TSAI; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Ras oncogenes are the most frequently mutated in human cancer. The Ras proteins are small GTPases that control critical cellular pathways for growth, proliferation, and survival, dysregulation of which ..
  30. CAAX Protein Processing and Cancer Therapy
    Stephen Young; Fiscal Year: 2007
    Proteins that terminate with a "CAAX" sequence motif (e.g., the Ras proteins, Rho proteins, and nuclear lamins) undergo three sequential posttranslational modifications...
  31. CAAX Processing Enzymes as Anticancer Targets
    Stephen Young; Fiscal Year: 2005
    ..Inhibitors of FTase have been used to treat cancers that harbor mutationally activated Ras proteins. Unfortunately, K-Ras and N-Ras--the Ras isoforms most often implicated in human cancers--are readily ..
  32. ROLE OF PROTO-ONCOGENES IN CELLULAR PROLIFERATION
    Dennis Stacey; Fiscal Year: 1993
    ..The consequences of this treatment upon the proliferative capacity of the cell then indicated the function of ras proteins in normal proliferation...
  33. JUN Kinase Signaling in the Lung
    Glenn Rosen; Fiscal Year: 2006
    The small GTPase Ras proteins play an essential role in transducing extracellular signals that regulate cell growth, survival, and differentiation...
  34. NOVEL SECOND MESSENGER SIGNALING IN THE STRIATUM
    ANN GRAYBIEL; Fiscal Year: 2003
    b>Ras proteins are key regulators of growth and differentiation, but recently have also been implicated in learning and memory functions in the brain...
  35. Atorvastatin, a prenylation inhibitor in acute leukemia.
    Raymond Perez; Fiscal Year: 2003
    b>Ras proteins are critically involved in transformation, proliferation, and survival of malignant cells, including blasts from patients with acute leukemia and myelodysplasia...
  36. G PROTEIN-MEDIATED NUTRITIONAL SIGNALING IN YEAST
    JEANNE HIRSCH; Fiscal Year: 2003
    ..Nutritional signaling involves the activation of Ras proteins and adenylyl cyclase through a process that is not well understood...
  37. PRENYLATION OF ONCOGENIC PTPCAAX TYROSINE PHOSPHATASES
    Pamela Crowell; Fiscal Year: 1999
    DESCRIPTION: Many prenylated proteins (e.g. the ras proteins) play important roles in cellular signal transduction, and prenylation is obligatory for their proper subcellular localization and function...
  38. RIN1, A NOVEL RAS-INHIBITORY PROTEIN IN YEAST
    David Levin; Fiscal Year: 2006
    ..b>Ras proteins are highly conserved among eukaryotic species...
  39. RAS PROTEINS IN T CELL ACTIVATION AND DIFFERENTIATION
    Jan Czyzyk; Fiscal Year: 2002
    ..In addition, basic studies on the regulation of T lymphocytes by small GTPases have broad applicability to the field of cancer pathogenesis. ..
  40. COLONIC EPITHELIAL CELL PLASMA MEMBRANES
    Thomas Brasitus; Fiscal Year: 1999
    ..Although highly regulated in normal tissue, the Ras proteins can be constitutively activated by several mechanisms that enhance their transforming ability in colonocytes...
  41. Inhibitors of Human Pal mitoyl Acyltransferase
    CHARLES DUCKER; Fiscal Year: 2005
    ..Since post-translational processing of Ras proteins is critical for their function, the enzymes that catalyze these processing steps have been considered as ..
  42. STRUCTURE AND BIOLOGY OF RAS PROTEINS IN CANCER
    Sharon Campbell; Fiscal Year: 1999
    The main objective of this proposal is to better understand how Ras proteins function as molecular switches that are controlled by a regulated GDP/GTP cycle...
  43. FUNCTION OF THE EVOLUTIONARILY CONSERVED RHO GENE FAMILY
    ALAN MYERS; Fiscal Year: 1992
    ..The implied structural similarity of rho and ras proteins suggests that the two families evolved from a common ancestral gene, and that the proteins share common ..
  44. RAS-SPECIFIC T CELL MEDIATED IMMUNOTHERAPY
    MARTIN CHEEVER; Fiscal Year: 2000
    ..Mutations in ras oncogenes are usually single nucleotide substitutions that result in the expression of ras proteins with single amino acid substitutions...
  45. SIGNAL TRANSDUCTION BY CELLULAR PROTOONCOGENES
    James Feramisco; Fiscal Year: 1992
    ..to evaluate the biological and biochemical changes that occur in living cells microinjected with the purified ras proteins or with neutralizing antibodies directed against these proteins...
  46. Structure/Function Analysis of Icmt
    MARK REID PHILIPS; Fiscal Year: 2010
    ..Accordingly, Ras is an attractive target for anti- cancer drug discovery. Ras proteins are GTPases that are biologically active only when associated with cellular membranes...
  47. Ras signaling in leukemogenesis
    Ruibao Ren; Fiscal Year: 2010
    b>Ras proteins are crucial regulators of cell proliferation, survival and differentiation...
  48. Defective Processing of the CaaX Motif in Ras Proteins
    DIANA SMITH BECKERMAN; Fiscal Year: 2001
    DESCRIPTION (provided by applicant) Ras proteins play an important role in transporting signals from membrane receptors of growth factors to the nucleus, triggering transcription of genes involved in cellular proliferation...
  49. FUNCTION AND EVOLUTION OF RAS PROTEINS
    Michael Wigler; Fiscal Year: 1990
    ..There has been recent and striking progress in our understanding of the RAS proteins, and much more can be anticipated in the coming year, including: an understanding of effector function for RAS ..
  50. STRUCTURAL CHANGES AND THE FUNCTION OF RAS ONCOGENES
    Robert J Deschenes; Fiscal Year: 2010
    b>Ras proteins are evolutionarily conserved, membrane-associated, small GTP binding proteins involved in signal transduction pathways...
  51. Design of Membrane-Associated Signaling Modulators
    James Tam; Fiscal Year: 2003
    b>Ras proteins are membrane-associated proteins that modulate cell activation by acting as a molecular "on-off" switch of many receptor-coupled signaling pathways...
  52. GENETIC ANALYSIS OF THE UPSTREAM CONTROL OF YEAST RAS
    Scott Powers; Fiscal Year: 1993
    ..In order to gain more insight into the control of the activity of Ras proteins, we propose to continue our search for novel regulators of Ras protein activity in the model eukaryotic cell, ..
  53. MOLECULAR GENETICS OF THE G PROTEIN-TARGET INTERACTION
    Tohru Kataoka; Fiscal Year: 1990
    ..In the yeast cyclase system our aim will be to analyse the precise mode of interaction between ras proteins and cyclase, and also to define a structural element in cyclase which is responsible for the interaction with ..
  54. ONCOGENE SPECIFICITY IN ORGAN-DEFINED CANCERS
    Michael Gould; Fiscal Year: 2001
    ..in the Ras protein itself, Aim 1 will test the hypothesis that subtle differences in the carboxyl end of the Ras proteins (H- or K-Ras) modify Ras membrane localization, leading to tumor-type specificity...
  55. Mapping the Binding Surfaces of Ras and Related GTPases
    Carla Mattos; Fiscal Year: 2007
    ..will be used in the future to guide the design of specific ligands targeted towards the defective oncogenic Ras proteins. Our approach is based on a comparative analysis of the binding surfaces of Ras, two of its most common ..
  56. Ras Peptide Aptamers
    WILSON XU; Fiscal Year: 2009
    Mutations in codon 12, 13, or 61 convert H-ras, K-ras, and N-ras into oncogenes. Such mutationally activated Ras proteins are found in about 30% of human tumors...
  57. FASEB Summer Research Conference on Small G-Proteins
    Jeffrey Settleman; Fiscal Year: 2004
    ..This family includes, among others, the Ras proteins, which have been studied intensively in the context of human oncogenesis, the Rho proteins, that function as ..
  58. Genetics of RAS, PTEN, BRAF and CDKN2A in Melanoma
    Philip Hinds; Fiscal Year: 2009
    ..b>RAS proteins mediate their effects biochemically through several downstream pathways, but most importantly through the ..
  59. RAS INDUCED GENE EXPRESSION AND MALIGNANT TRANSFORMATION
    CRAIG HAUSER; Fiscal Year: 2002
    Aberrant Ras function contributes to the development of a wide spectrum of human cancers. Mutated Ras proteins cause deregulated signaling to the nucleus and stimulation of cell proliferation...
  60. Development of an ICMT Supported Membrane Sensor
    David Thompson; Fiscal Year: 2009
    ..screening drug libraries for lead compounds that are likely to inhibit the methylation of cellular oncogenic Ras proteins. Discovery and development of these compounds are important because inhibition of Ras carboxylmethylation ..
  61. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  62. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  63. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..