RASGRP1

Summary

Gene Symbol: RASGRP1
Description: RAS guanyl releasing protein 1
Alias: CALDAG-GEFI, CALDAG-GEFII, RASGRP, hRasGRP1, RAS guanyl-releasing protein 1, RAS guanyl nucleotide-releasing protein 1, RAS guanyl releasing protein 1 (calcium and DAG-regulated), calcium and DAG-regulated guanine nucleotide exchange factor II, calcium- and diacylglycerol-regulated guanine nucleotide exchange factor II, guanine nucleotide exchange factor, calcium- and DAG-regulated, Rap1A, ras activator RasGRP
Species: human

Top Publications

  1. ncbi RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs
    J O Ebinu
    Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Science 280:1082-6. 1998
  2. ncbi Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1
    Trever G Bivona
    Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
    Nature 424:694-8. 2003
  3. doi MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1
    Wen Pan
    Joint Molecular Rheumatology Laboratory, Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai, China
    J Immunol 184:6773-81. 2010
  4. pmc G alpha i2 and ZAP-70 mediate RasGRP1 membrane localization and activation of SDF-1-induced T cell functions
    Kimberly N Kremer
    Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Immunol 187:3177-85. 2011
  5. pmc Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes
    Struan F A Grant
    Center for Applied Genomics, Abramson Research Center, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Diabetes 58:290-5. 2009
  6. pmc A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia
    H Kawasaki
    Department of Brain and Cognitive Sciences, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 95:13278-83. 1998
  7. ncbi RasGRP links T-cell receptor signaling to Ras
    J O Ebinu
    Departments of Biochemistry and Immunobiology, University of Alberta, Edmonton, Canada
    Blood 95:3199-203. 2000
  8. ncbi CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation
    Jill R Crittenden
    Department of Brain and Cognitive Sciences, and McGovern Institute for Brain Research, Massachusetts Institute of Technology, 45 Carleton Street, E25 618, Cambridge, Massachusetts 02139, USA
    Nat Med 10:982-6. 2004
  9. ncbi Deregulated expression of RasGRP1 initiates thymic lymphomagenesis independently of T-cell receptors
    Mark B Klinger
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
    Oncogene 24:2695-704. 2005
  10. pmc A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells
    Jeroen P Roose
    Department of Medicine, UCSF, 533 Parnassus Avenue, Room U 330, San Francisco, CA 94143, USA
    Mol Cell Biol 25:4426-41. 2005

Research Grants

  1. Novel Molecules in Calcium Signaling in Platelets
    Wolfgang Bergmeier; Fiscal Year: 2013
  2. Mechanistic Studies of Ras-MAPK Signals: Specialzed Cues for the T cell Lineage?
    Jeroen Roose; Fiscal Year: 2011
  3. Differential regulation of Ras nucleotide exchange factors
    JEFFREY SCOTT IWIG; Fiscal Year: 2012
  4. NOVEL SECOND MESSENGER SIGNALING IN THE STRIATUM
    Ann M Graybiel; Fiscal Year: 2013
  5. Arthur Weiss; Fiscal Year: 2016
  6. NOVEL SECOND MESSENGER SIGNALING IN THE STRIATUM
    ANN GRAYBIEL; Fiscal Year: 2003
  7. JOE WILLIAM RAMOS; Fiscal Year: 2015
  8. Compartment Specific Signaling of Ras
    MARK REID PHILIPS; Fiscal Year: 2010
  9. Fine Mapping and Functional Evaluation of Selected Type 1 Diabetes Loci
    Hakon Hakonarson; Fiscal Year: 2009
  10. RasGRP4-dependent Responses in Mast Cells
    Richard Stevens; Fiscal Year: 2009

Scientific Experts

Detail Information

Publications146 found, 100 shown here

  1. ncbi RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs
    J O Ebinu
    Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Science 280:1082-6. 1998
    b>RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized...
  2. ncbi Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1
    Trever G Bivona
    Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
    Nature 424:694-8. 2003
    ..in response to Src-dependent activation of phospholipase Cgamma1, the Ras guanine nucleotide exchange factor RasGRP1 translocated to the Golgi where it activated Ras...
  3. doi MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1
    Wen Pan
    Joint Molecular Rheumatology Laboratory, Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai, China
    J Immunol 184:6773-81. 2010
    ..revealed that miR-21 indirectly downregulated DNMT1 expression by targeting an important autoimmune gene, RASGRP1, which mediated the Ras-MAPK pathway upstream of DNMT1; miR-148a directly downregulated DNMT1 expression by ..
  4. pmc G alpha i2 and ZAP-70 mediate RasGRP1 membrane localization and activation of SDF-1-induced T cell functions
    Kimberly N Kremer
    Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Immunol 187:3177-85. 2011
    b>RasGRP1, a Ras guanine-nucleotide exchange factor, critically mediates T cell development and function and controls immunodeficiency and autoimmunity...
  5. pmc Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes
    Struan F A Grant
    Center for Applied Genomics, Abramson Research Center, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Diabetes 58:290-5. 2009
    ....
  6. pmc A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia
    H Kawasaki
    Department of Brain and Cognitive Sciences, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 95:13278-83. 1998
    ..By contrast, CalDAG-GEFII, a second CalDAG-GEF family member that we cloned and found identical to RasGRP [Ebinu, J. O., Bottorff, D. A., Chan, E. Y. W., Stang, S. L., Dunn, R. J. & Stone, J. C...
  7. ncbi RasGRP links T-cell receptor signaling to Ras
    J O Ebinu
    Departments of Biochemistry and Immunobiology, University of Alberta, Edmonton, Canada
    Blood 95:3199-203. 2000
    ..Here we show that RasGRP, a Ras activator that contains calcium-binding EF hands and a DAG-binding domain, is expressed in T cells...
  8. ncbi CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation
    Jill R Crittenden
    Department of Brain and Cognitive Sciences, and McGovern Institute for Brain Research, Massachusetts Institute of Technology, 45 Carleton Street, E25 618, Cambridge, Massachusetts 02139, USA
    Nat Med 10:982-6. 2004
    ..However, an alternative pathway may involve members of the CalDAG-GEF/RasGRP protein family, which have structural features (calcium-binding EF hands and DAG-binding C1 domains) that suggest ..
  9. ncbi Deregulated expression of RasGRP1 initiates thymic lymphomagenesis independently of T-cell receptors
    Mark B Klinger
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
    Oncogene 24:2695-704. 2005
    b>RasGRP1 is a Ras-specific exchange factor, which is activated by T-cell receptor (TCR) and promotes TCR-dependent positive selection of thymocytes...
  10. pmc A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells
    Jeroen P Roose
    Department of Medicine, UCSF, 533 Parnassus Avenue, Room U 330, San Francisco, CA 94143, USA
    Mol Cell Biol 25:4426-41. 2005
    ..In T lymphocytes, Ras can be activated by two Ras exchange factors, SOS and RasGRP1, which are recruited through the adapters Grb2 and LAT and via the second-messenger diacylglycerol (DAG), ..
  11. pmc An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response
    Yan Liu
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Exp Med 204:93-103. 2007
    ..Here, we report that RasGRP1 plays an important role in FcepsilonRI-mediated PI3K activation and mast cell function...
  12. pmc Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes
    Jeroen P Roose
    Department of Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143 0795, USA
    Mol Cell Biol 27:2732-45. 2007
    ..In addition, RasGRP1 appears to be dominant over SOS in an unknown manner...
  13. pmc Association of RASGRP1 with type 1 diabetes is revealed by combined follow-up of two genome-wide studies
    H Q Qu
    J Med Genet 46:553-4. 2009
    ....
  14. pmc RasGRP1 is required for human NK cell function
    Suk Hyung Lee
    Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong Gu, Daejeon, Republic of Korea
    J Immunol 183:7931-8. 2009
    ..We now report that RasGRP1, which can also be detected in human NK cells, plays an essential role in NK cell effector functions...
  15. pmc Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases
    Vincent Plagnol
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom
    PLoS Genet 7:e1002216. 2011
    ..10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA...
  16. doi Aberrant expression of RasGRP1 cooperates with gain-of-function NOTCH1 mutations in T-cell leukemogenesis
    T Oki
    Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Leukemia 26:1038-45. 2012
    ..Previous studies have indicated the possible involvement of RasGRP1 and RasGRP4 in leukemogenesis. Here, the predominant role of RasGRP1 in T-cell leukemogenesis is clarified...
  17. ncbi Defective expression of Ras guanyl nucleotide-releasing protein 1 in a subset of patients with systemic lupus erythematosus
    Shinsuke Yasuda
    Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    J Immunol 179:4890-900. 2007
    Dysregulation of Ras guanyl nucleotide-releasing protein 1 (RasGRP1) in mice results in a systemic lupus erythematosus (SLE)-like disorder...
  18. ncbi Calcium-diacylglycerol guanine nucleotide exchange factor I gene mutations associated with loss of function in canine platelets
    Mary K Boudreaux
    Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849 5519, USA
    Transl Res 150:81-92. 2007
    ....
  19. ncbi Guanine nucleotide exchange factors CalDAG-GEFI and CalDAG-GEFII are colocalized in striatal projection neurons
    S Toki
    Pharmaceutical Research Institute, Kyowa Hakko Kogyo Company, Ltd, Shizuoka 411 8731, Japan
    J Comp Neurol 437:398-407. 2001
    CalDAG-GEFI and CalDAG-GEFII (identical to RasGRP) are novel, brain-enriched guanine nucleotide exchange factors (GEFs) that can be stimulated by calcium and diacylglycerol and that can activate small GTPases, including Ras and Rap1, ..
  20. pmc Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta
    Sung Hee Choi
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:10543-9. 2008
    ..by protein kinase C (PKC) and by several other families of signal-transducing proteins such as the chimerins or RasGRP. MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase), a member of the dystrophia myotonica protein ..
  21. doi Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditions
    Eugenia Manevich-Mendelson
    Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
    Blood 114:2344-53. 2009
    ..Deletion of the putative beta(1) Kindlin-3 binding site also retained VLA-4 adhesiveness. Thus, our study provides the first evidence that Kindlin-3 is more critical to LFA-1 than to VLA-4-adhesive functions in human lymphocytes...
  22. ncbi Characterization of GFR, a novel guanine nucleotide exchange factor for Rap1
    T Ichiba
    Department of Internal Medicine 3, Jikei University, School of Medicine, Tokyo, Japan
    FEBS Lett 457:85-9. 1999
    ..Northern blot analysis suggested that GFR mRNA is strongly expressed in the brain. In transfected HeLa cells, GFR has been found to be localized in the nuclei...
  23. ncbi Phorbol esters modulate the Ras exchange factor RasGRP3
    P S Lorenzo
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    Cancer Res 61:943-9. 2001
    b>RasGRP represents the prototype of a new class of guanine nucleotide exchange factors that activate small GTPases...
  24. ncbi Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1
    Koko Katagiri
    Bayer chair Department of Molecular Immunology and Allergy and Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Biol Chem 279:11875-81. 2004
    ..Our results demonstrate that TCR activation of Rap1 depends on PLC-gamma1. This activity is likely to be mediated by CalDAG-GEFI, which is required to activate LFA-1...
  25. pmc Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III
    Wolfgang Bergmeier
    CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 117:1699-707. 2007
    ..Thus, mice engineered to lack CalDAG-GEFI have a combination of defects in leukocyte and platelet functions similar to that of LAD-III patients...
  26. ncbi RasGRP4 is a novel Ras activator isolated from acute myeloid leukemia
    Gary W Reuther
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    J Biol Chem 277:30508-14. 2002
    ..We identified a new member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors, designating it RasGRP4...
  27. ncbi The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2
    Adam Mor
    Department of Medicine, NYU School of Medicine, New York, NY 10016, USA
    Nat Cell Biol 9:713-9. 2007
    ..Ras activation on both compartments required RasGRP1, an exchange factor regulated by calcium and diacylglycerol (DAG), but phospholipase C (PLC) activity was ..
  28. doi Membrane localization of RasGRP1 is controlled by an EF-hand, and by the GEF domain
    Ghazaleh Tazmini
    Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver BC, Canada
    Biochim Biophys Acta 1793:447-61. 2009
    b>RasGRP1 is an exchange factor for membrane-localized Ras GTPases. Activation of RasGRP1 requires its translocation to membranes, which can be directly mediated by either its PT or C1 domains...
  29. pmc Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras
    Jennifer O Lauchle
    Department of Pediatrics, University of California, San Francisco, California 94143, USA
    Nature 461:411-4. 2009
    ..We cloned clone-specific retroviral integrations to identify candidate resistance genes including Rasgrp1, Rasgrp4 and Mapk14, which encodes p38alpha...
  30. ncbi T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha
    Yuanyuan Zha
    Department of Pathology, Section of Hematology and Oncology, University of Chicago, Chicago, Illinois 60637, USA
    Nat Immunol 7:1166-73. 2006
    ..overexpression were associated with defective translocation of the Ras guanine nucleotide-exchange factor RasGRP1 to the plasma membrane...
  31. pmc Transgenic overexpression of RasGRP1 in mouse epidermis results in spontaneous tumors of the skin
    Carolyn E Oki-Idouchi
    Natural Products and Cancer Biology Program, Cancer Research Center of Hawaii, University of Hawaii at Manoa, 651 Ilalo Street, Honolulu, HI 96813, USA
    Cancer Res 67:276-80. 2007
    b>RasGRP1 is a guanine nucleotide exchange factor for Ras and a receptor of the second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters...
  32. doi CalDAG-GEFI is at the nexus of calcium-dependent platelet activation
    Lucia Stefanini
    Cardeza Foundation and Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19007, USA
    Blood 114:2506-14. 2009
    ....
  33. ncbi Iridals are a novel class of ligands for phorbol ester receptors with modest selectivity for the RasGRP receptor subfamily
    L Shao
    Drug Discovery Program, University of Michigan Cancer Center, Department of Internal Medicine, University of Michigan, 1500 E Medical Center Drive, Ann Arbor, Michigan 48109 0934, USA
    J Med Chem 44:3872-80. 2001
    ..We conclude that the iridals represent a promising structural motif for design of ligands for phorbol ester receptor family members...
  34. pmc The small GTPase Rap1b regulates the cross talk between platelet integrin alpha2beta1 and integrin alphaIIbbeta3
    Bruno Bernardi
    Department of Biochemistry, University of Pavia, via Bassi 21, 27100 Pavia, Italy
    Blood 107:2728-35. 2006
    ..These results demonstrate that Rap1b is an important element in integrin-dependent outside-in signaling during platelet adhesion and regulates the cross talk between adhesive receptors...
  35. pmc Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy
    Jill R Crittenden
    Department of Brain and Cognitive Sciences and the McGovern Institute for Brain Research, Massachusetts Institute of Technology, 43 Vassar Street, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 106:2892-6. 2009
    ..kinase signal transduction cascade, matrix-enriched CalDAG-GEFI and striosome-enriched CalDAG-GEFII (also known as RasGRP), are strongly and inversely dysregulated in proportion to the severity of abnormal movements induced by l-DOPA in ..
  36. ncbi Regulation of T cell receptor-induced activation of the Ras-ERK pathway by diacylglycerol kinase zeta
    Xiao Ping Zhong
    Signal Transduction Program, The Abramson Family Cancer Research Institute, Immunology Graduate Program, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    J Biol Chem 277:31089-98. 2002
    ..DAG activates RasGRP and protein kinase C theta...
  37. pmc Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus
    Ignacio Perez de Castro
    Department of Pathology and New York University Cancer Institute, New York, New York 10016, USA
    Mol Cell Biol 24:3485-96. 2004
    ..Ras, revealed that N-Ras activation occurs exclusively on the Golgi apparatus in a phospholipase Cgamma- and RasGRP1-dependent fashion...
  38. ncbi Pharmacology of the receptors for the phorbol ester tumor promoters: multiple receptors with different biochemical properties
    M G Kazanietz
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, 19104 6160, USA
    Biochem Pharmacol 60:1417-24. 2000
    ..These novel receptors lacking kinase activity include chimaerins (a family of Rac-GTPase-activating proteins), RasGRP (a Ras exchange factor), and Unc-13/Munc-13 (a family of proteins involved in exocytosis)...
  39. ncbi Intracellular signaling in platelets
    Charles S Abrams
    University of Pennsylvania, Room 912, Biomedical Research Building II III, 421 Curie Blvd, Philadelphia, PA 19104, USA
    Curr Opin Hematol 12:401-5. 2005
    ..Over the past few years, a large portion of platelet research has focused on intracellular signaling events that contribute to stable platelet adhesion and aggregation...
  40. ncbi The role of RasGRPs in regulation of lymphocyte proliferation
    Jason J Coughlin
    Department of Biochemistry, University of Alberta, Edmonton, Alta, Canada T6G 2H7
    Immunol Lett 105:77-82. 2006
    b>RasGRP1 links TCR signaling to Ras in T cells, while both RasGRP1 and RasGRP3 link BCR signaling to Ras in B cells...
  41. pmc Differential membrane binding and diacylglycerol recognition by C1 domains of RasGRPs
    Joanne E Johnson
    Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada, V5A 1S6
    Biochem J 406:223-36. 2007
    ..This has been demonstrated for RasGRP1 and RasGRP3, but has not been tested directly for RasGRP2, RasGRP4alpha and RasGRP4beta...
  42. ncbi Preferential development of CD4 and CD8 T regulatory cells in RasGRP1-deficient mice
    Xiaoxi Chen
    Department of Microbiology and Immunology, Life Science Centre, University of British Columbia, 2350 Health Science Mall, Vancouver, BC, Canada
    J Immunol 180:5973-82. 2008
    b>RasGRP1 and Sos are two Ras-guanyl-nucleotide exchange factors that link TCR signal transduction to Ras and MAPK activation...
  43. ncbi RasGRP1 represents a novel non-protein kinase C phorbol ester signaling pathway in mouse epidermal keratinocytes
    Reshmi A Rambaratsingh
    Natural Products Program, Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, USA
    J Biol Chem 278:52792-801. 2003
    ..We documented expression of the high affinity non-PKC phorbol ester receptor and Ras activator RasGRP1 in mouse primary keratinocytes...
  44. ncbi RasGRP1 transmits prodifferentiation TCR signaling that is crucial for CD4 T cell development
    John J Priatel
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
    J Immunol 177:1470-80. 2006
    ..orchestrates the activation of Ras by integrating at least two Ras-guanyl nucleotide exchange factors, RasGRP1 and Sos...
  45. ncbi Expression of a catalytically inactive form of diacylglycerol kinase alpha induces sustained signaling through RasGRP
    David R Jones
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Cantoblanco, E 28049 Madrid, Spain
    FASEB J 16:595-7. 2002
    ..causes rapid, transient membrane translocation of the recently discovered Ras guanyl nucleotide release protein (RasGRP), followed by activation of mitogen-activated protein kinase (MAPK)...
  46. ncbi RasGRP1 transduces low-grade TCR signals which are critical for T cell development, homeostasis, and differentiation
    John J Priatel
    Department of Microbiology and Immunology, University of British Columbia, Vancouver V6T 1Z3, Canada
    Immunity 17:617-27. 2002
    Two important Ras-guanyl nucleotide exchange factors, Sos and RasGRP1, control Ras activation in thymocytes...
  47. ncbi Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos, and RasGRP1
    Lucinda F Reynolds
    Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 279:18239-46. 2004
    ..First, Vav1 transduces signals via phospholipase Cgamma1 leading to the membrane recruitment of RasGRP1. Second, Vav1 is required for recruitment of Sos1 and -2 to the transmembrane adapter protein LAT...
  48. ncbi Inverted signaling hierarchy between RAS and RAC in T-lymphocytes
    José L Zugaza
    Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, University of Salamanca CSIC, Campus Unamuno, E 37007 Salamanca, Spain
    Oncogene 23:5823-33. 2004
    ..The molecular link for this new type of pathway interconnectivity is RasGRP1, a diacylglycerol-dependent GDP/GTP exchange factor for Ras that translocates to the plasma membrane in a Vav- ..
  49. ncbi PKCdelta associates with and is involved in the phosphorylation of RasGRP3 in response to phorbol esters
    Chaya Brodie
    Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel
    Mol Pharmacol 66:76-84. 2004
    b>RasGRP is a family of guanine nucleotide exchange factors that activate small GTPases and contain a C1 domain similar to the one present in protein kinase C (PKC)...
  50. ncbi RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor-Ras signaling
    Jason J Coughlin
    Department of Biochemistry, University of Alberta, Edmonton, Canada
    J Immunol 175:7179-84. 2005
    The RasGRPs are a family of Ras activators that possess diacylglycerol-binding C1 domains. In T cells, RasGRP1 links TCR signaling to Ras. B cells coexpress RasGRP1 and RasGRP3...
  51. ncbi Regulation of Ras in lymphocytes: get a GRP
    J C Stone
    Department of Biochemistry, University of Alberta, Edmonton, AB, Canada T6G 2H7
    Biochem Soc Trans 34:858-61. 2006
    ..b>RasGRP1 possesses a catalytic region consisting of a REM (Ras exchange motif) and a CDC25 (cell division cycle 25) domain...
  52. pmc A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets
    Ronit Pasvolsky
    Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Exp Med 204:1571-82. 2007
    ..Chemokine-triggered VLA-4 adhesiveness in T lymphocytes was partially defective as well. These studies identify CalDAG-GEFI as a critical regulator of inside-out integrin activation in human T lymphocytes, neutrophils, and platelets...
  53. pmc Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion
    Haifa Ghandour
    Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Blood 110:3682-90. 2007
    ..Thus, PLC/CalDAG-GEFI regulation of Rap1 is selectively required for chemokine- and PMA-induced LFA-1 activation in human T cells, whereas alternate PLC- and PKC-dependent mechanisms are involved in the regulation of VLA-4...
  54. ncbi [Gene screening in five Chinese families with hereditary spastic paraplegia with thin corpus callosum]
    Guo Hua Zhao
    Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008 PR China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 24:677-80. 2007
    ..To screen all ten genes between D15S971 and D15S1012 in five Chinese families with hereditary spastic paraplegia with thin corpus callosum (HSP-TCC)...
  55. doi Phase II trial and prediction of response of single agent tipifarnib in patients with relapsed/refractory mantle cell lymphoma: a Groupe d'Etude des Lymphomes de l'Adulte trial
    Delphine Rolland
    INSERM U836 Equipe 7, Faculte de Medecine, Universite Joseph Fourier, Grenoble, France
    Cancer Chemother Pharmacol 65:781-90. 2010
    ..We conducted a multicenter phase II study of a potent Ftase inhibitor, tipifarnib, in patients with relapsed or refractory MCL...
  56. doi RasGRP1 regulates antigen-induced developmental programming by naive CD8 T cells
    John J Priatel
    Child and Family Research Institute, Vancouver, British Columbia, Canada
    J Immunol 184:666-76. 2010
    ..The Ras-guanyl nucleotide exchange factor RasGRP1 has been shown to transduce TCR-mediated signals critically required for the maturation of developing thymocytes...
  57. pmc CalDAG-GEFI down-regulation in the striatum as a neuroprotective change in Huntington's disease
    Jill R Crittenden
    McGovern Institute for Brain Research, MIT, 43 Vassar Street, Building 46 6133, Cambridge, MA, USA
    Hum Mol Genet 19:1756-65. 2010
    ..These findings suggest that the striking down-regulation of CalDAG-GEFI in HD could be a protective mechanism that mitigates Htt-induced degeneration...
  58. pmc Negative regulation of mTOR activation by diacylglycerol kinases
    Balachandra K Gorentla
    Department of Pediatric Allergy and Immunology, Duke University Medical Center, Durham, NC, USA
    Blood 117:4022-31. 2011
    ..Deficiency of RasGRP1 or inhibition of Mek1/2 activity drastically decreases TCR-induced mTOR activation, whereas constitutively active ..
  59. pmc Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice
    George S Vassiliou
    Mouse Genomics Team, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
    Nat Genet 43:470-5. 2011
    ..rapid-onset AML in 80% of mice with Npm1c, associated with mutually exclusive integrations in Csf2, Flt3 or Rasgrp1 in 55 of 70 leukemias...
  60. pmc Critical roles of RasGRP1 for invariant NKT cell development
    Shudan Shen
    Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 187:4467-73. 2011
    ..b>RasGRP1, a guanine nucleotide exchange factor for TCR-induced activation of the Ras-ERK1/2 pathway, is critical for ..
  61. doi Signal transducer and activator of transcription 2 (STAT2) metabolism coupling postmitotic outgrowth to visual and sound perception network in human left cerebrum by biocomputation
    Lin Wang
    Biomedical Center, School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing, 100876, China
    J Mol Neurosci 47:649-58. 2012
    ..Our result showed that upstream RECQL, PDIA2, ENOSF1, THBS4, RASGRP1, PER2, PDE8A, ORC2L, DCI, OGG1_2, SMA4, GPD1, etc...
  62. doi A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets
    Jalal Taneera
    Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmo 20502, Sweden
    Cell Metab 16:122-34. 2012
    ..We integrated our data to form a rank list of putative T2D genes, of which CHL1, LRFN2, RASGRP1, and PPM1K were validated in INS-1 cells to influence insulin secretion, whereas GPR120 affected apoptosis in ..
  63. pmc The clinically relevant pharmacogenomic changes in acute myelogenous leukemia
    Ashkan Emadi
    University of Maryland, School of Medicine, Marlene and Stewart Greenebaum Cancer Center, Leukemia and Hematologic Malignancies, Baltimore, MD 21201, USA
    Pharmacogenomics 13:1257-69. 2012
    ..inhibitors, the authors also reviewed findings related to a two-gene transcript signature consisting of high RASGRP1 and low APTX, the ratio of which appears to positively predict clinical response in AML patients treated with ..
  64. pmc PI3-kinase γ promotes Rap1a-mediated activation of myeloid cell integrin α4β1, leading to tumor inflammation and growth
    Michael C Schmid
    Moores Cancer Center, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 8:e60226. 2013
    ..We show here that PI3Kγ activates PLCγ, leading to RasGrp/CalDAG-GEF-I&II mediated, Rap1a-dependent activation of integrin α4β1, extravasation of monocytes and ..
  65. ncbi Establishing genomic/transcriptomic links between Alzheimer's disease and type 2 diabetes mellitus by meta-analysis approach
    Zeenat Mirza
    Center of Excellence in Genomic Medicine Research, King Abdulaziz University, PO Box 80216, Jeddah, Pin 21589, Kingdom of Saudi Arabia
    CNS Neurol Disord Drug Targets 13:501-16. 2014
    ..05. Significantly changed expression of "myeloid leukemia cell differentiation protein 1; RAS guanyl releasing protein 1; S100 calcium-binding protein A8; prostaglandin- endoperoxide synthase 2; parvalbumin; endoplasmic ..
  66. pmc Mechanisms of interferon-γ production by neutrophils and its function during Streptococcus pneumoniae pneumonia
    John C Gomez
    1 Center for Airways Disease, Department of Medicine
    Am J Respir Cell Mol Biol 52:349-64. 2015
    ..These studies underline the complexity of the neutrophil responses during pneumonia in the acute inflammatory response and in subsequent resolution or initiation of immune responses. ..
  67. pmc RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and restricts intestinal epithelial cell growth
    Philippe Depeille
    Department of Anatomy, University of California, San Francisco, San Francisco, California 94143, USA
    Nat Cell Biol 17:804-15. 2015
    ..Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of EGFR but act in functional opposition...
  68. pmc RAP1-GTPase signaling and platelet function
    Lucia Stefanini
    Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, UK
    J Mol Med (Berl) 94:13-9. 2016
    ..This review will summarize important studies that elucidated the signaling pathways that control RAP1 activation in platelets. ..
  69. pmc High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry
    Celi Sun
    Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
    Nat Genet 48:323-30. 2016
    ..75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6...
  70. pmc CalDAG-GEFI Deficiency Reduces Atherosclerotic Lesion Development in Mice
    Yacine Boulaftali
    From the McAllister Heart Institute and Department of Medicine Y B, A P O, A B, R P, C C, R H L, D S P, N M, W B, Department of Biochemistry and Biophysics W B, University of North Carolina at Chapel Hill and Portola Pharmaceuticals, South San Francisco, CA P B C
    Arterioscler Thromb Vasc Biol 36:792-9. 2016
    ..In this study, we evaluated lesion formation in atherosclerosis-prone low-density lipoprotein receptor deficient (Ldlr(-/-)) mice lacking CDGI or P2Y12 in hematopoietic cells...
  71. ncbi Association of established thyroid peroxidase autoantibody (TPOAb) genetic variants with Hashimoto's thyroiditis
    Luka Brcic
    a Department of Medical Biology, School of Medicine, University of Split, Split, Croatia
    Autoimmunity 49:480-485. 2016
    ..0149, OR = 0.73, CI = 0.56-0.94), rs7171171 near RASGRP1 gene (p = 0.0356, OR = 1.4, CI = 1.02-1.92) and rs11675434 in TPO gene (p = 0.041, OR = 1...
  72. pmc Mice Expressing Low Levels of CalDAG-GEFI Exhibit Markedly Impaired Platelet Activation With Minor Impact on Hemostasis
    Raymond Piatt
    From the McAllister Heart Institute, University of North Carolina, Chapel Hill R P, D S P, R H L, W B Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA S E M Department of Biochemistry and Biophysics L V P, W B, Animal Models Core D O C, and Rodent Advanced Surgical Core B C C, University of North Carolina at Chapel Hill
    Arterioscler Thromb Vasc Biol 36:1838-46. 2016
    ..In this study, we investigated whether low-level expression of CD-GEFI leads to protection from thrombosis without pathological bleeding in mice...
  73. ncbi Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans
    Jing Dong
    Epidemiology Branch, National Institute of Environmental Health Sciences, 111 T W Alexander Dr P O Box 12233, Mail Drop A3 05, Research Triangle Park, NC, 27709, USA
    Mol Neurobiol . 2016
    ..In the EA population, we identified two novel loci in or near RASGRP1 and ANXA2P3 associated with sense of smell...
  74. ncbi Structural basis of RasGRP binding to high-affinity PKC ligands
    Suo Bao Rong
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970 Reservoir Road, Washington, D C 20007, USA
    J Med Chem 45:853-60. 2002
    The Ras guanyl releasing protein RasGRP belongs to the CDC25 class of guanyl nucleotide exchange factors that regulate Ras-related GTPases. These GTPases serve as switches for the propagation and divergence of signaling pathways...
  75. ncbi Role of phorbol ester localization in determining protein kinase C or RasGRP3 translocation: real-time analysis using fluorescent ligands and proteins
    Derek C Braun
    Department of Biology, Gallaudet University, Washington, District of Columbia, USA
    Mol Cancer Ther 4:141-50. 2005
    The diacylglycerol signaling pathway, involving protein kinase C (PKC) and RasGRP, is a promising therapeutic target for both cancer and other indications...
  76. ncbi A novel diacylglycerol-lactone shows marked selectivity in vitro among C1 domains of protein kinase C (PKC) isoforms alpha and delta as well as selectivity for RasGRP compared with PKCalpha
    Yongmei Pu
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 280:27329-38. 2005
    ..In LNCaP cells, 130C037 likewise selectively induced membrane translocation of deltaC1b. 130C037 bound intact RasGRP1 and RasGRP3 with Ki values of 3.5 and 3...
  77. pmc Differential effects of bryostatin 1 and 12-O-tetradecanoylphorbol-13-acetate on the regulation and activation of RasGRP1 in mouse epidermal keratinocytes
    Matthew C Tuthill
    Natural Products and Cancer Biology Program, Cancer Research Center of Hawaii, University of Hawaii at Manoa, Room 315, 1236 Lauhala Street, Honolulu, HI 96813, USA
    Mol Cancer Ther 5:602-10. 2006
    ..We recently reported that the novel DAG receptor RasGRP1 is expressed in mouse keratinocytes and mediates TPA-induced Ras activation...
  78. ncbi Activation of Ras proteins by Ras guanine nucleotide releasing protein family members
    Que T Lambert
    H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida, USA
    Methods Enzymol 407:82-98. 2006
    ..Analyzing the regulation of RasGRP activity should continue to play an important role in understanding the mechanisms by which signal transduction ..
  79. doi Multiple checkpoint breach of B cell tolerance in Rasgrp1-deficient mice
    Amber Bartlett
    Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688
    J Immunol 191:3605-13. 2013
    ..Mice deficient in guanine nucleotide exchange factor Rasgrp1 develop a lymphoproliferative disorder with features of human systemic lupus erythematosus...
  80. pmc PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus
    Ting Jin
    Key Laboratory of Nutrition and Metabolism, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
    Cell Res 22:661-76. 2012
    ..Intriguingly, PAQR10 and PAQR11 are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1...
  81. pmc The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development
    Minghua Zhu
    Department of Immunology, Duke University, Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 287:8135-43. 2012
    ..The RasGRP family has four members. Published studies demonstrate that RasGRP1, RasGRP2, and RasGRP3 play critical roles in T cells, platelets, and B cells, respectively...
  82. pmc The role and regulation of mTOR in T-lymphocyte function
    Thomas F O'Brien
    Department of Pediatrics Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA
    Arch Immunol Ther Exp (Warsz) 60:173-81. 2012
    ..the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling.
  83. pmc TLR2 signaling subpathways regulate TLR9 signaling for the effective induction of IL-12 upon stimulation by heat-killed Brucella abortus
    Chun Yan Zhang
    Department of Immunology, Medical School, Nankai University, Tianjin, China
    Cell Mol Immunol 9:324-33. 2012
    ..Furthermore, Ras-guanine nucleotide-releasing protein 1 (RasGRP1) mediated the TLR2-induced ERK1/2 activation and inhibition of IL-12p40 production...
  84. doi P-glycoprotein (ABCB1) inhibited network of mitochondrion transport along microtubule and BMP signal-induced cell shape in chimpanzee left cerebrum by systems-theoretical analysis
    Hong Lin
    Biomedical Center, School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing, China
    Cell Biochem Funct 30:582-7. 2012
    ..and signal upstream network RAB2A inhibited ABCB1, and downstream ABCB1-inhibited SMAD1_2, NCK2, SLC25A46, GDF10, RASGRP1, EGFR, LRPPRC, RASSF2, RASA4, CA2, CBLB, UBR5, SLC25A16, ITGB3BP, DDIT4, PDPN, RAB2A in chimpanzee left cerebrum...
  85. pmc Regulation of RasGRP1 function in T cell development and activation by its unique tail domain
    Deirdre M Fuller
    Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS ONE 7:e38796. 2012
    The Ras-guanyl nucleotide exchange factor RasGRP1 plays a critical role in T cell receptor-mediated Erk activation...
  86. doi Is there a future for prenyltransferase inhibitors in cancer therapy?
    Sarah A Holstein
    Department of Internal Medicine, University of Iowa, C32 GH, Iowa City, IA 52242, USA
    Curr Opin Pharmacol 12:704-9. 2012
    ..Here we provide an update of the most recently published clinical trials, discuss the use of the RASGRP1/APTX two-gene expression screen to select patients with acute myeloid leukemia for therapy, and report on the ..
  87. doi LRRK2 expression is enriched in the striosomal compartment of mouse striatum
    Wim Mandemakers
    Center for Human Genetics, K U Leuven, Belgium
    Neurobiol Dis 48:582-93. 2012
    ..Interestingly, LRRK2 expression is associated with striosome specific markers (i.e. MOR1, RASGRP1)...
  88. pmc The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity
    Deirdre M Fuller
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 189:4005-13. 2012
    ..The deletion of the critical signaling proteins Gads and RasGRP1 caused a further block in thymocyte development, but, over time, could not prevent CD4(+) T cell ..
  89. ncbi Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3
    Y Ohba
    Department of Pathology, Research Institute, International Medical Center of Japan, 1 21 1 Toyama, Shinjuku ku, Tokyo 182 8655, Japan
    J Biol Chem 275:20020-6. 2000
    ..Guanine nucleotide exchange of R-Ras and TC21 was promoted by RasGRF, C3G, CalDAG-GEFI, CalDAG-GEFII (RasGRP), and CalDAG-GEFIII both in 293T cells and in vitro...
  90. ncbi Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor
    J Clyde-Smith
    Queensland Cancer Fund Laboratory of Experimental Oncology, Department of Pathology, University of Queensland Medical School, Herston Road, Brisbane 4006, Queensland, Australia
    J Biol Chem 275:32260-7. 2000
    ..Thus, under appropriate growth conditions, CalDAG-GEFI and RasGRP2 are dual specificity Ras and Rap exchange factors...
  91. ncbi RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demon
    Yi Yang
    Department of Medicine, Brigham and Women s Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:25756-74. 2002
    ..selectively express RasGRP4, and this new intracellular protein contains all of the domains present in the RasGRP family of guanine nucleotide exchange factors even though it is <50% identical to its closest homolog...
  92. pmc Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling
    Koji Eto
    Departments of Cell Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:12819-24. 2002
    ..01). These results establish that ES cells are a ready source of mature megakaryocytes for integrin studies and other biological applications, and they implicate CalDAG-GEFI in inside-out signaling to alphaIIbbeta3...
  93. ncbi Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters
    Nils Brose
    Abteilung Molekulare Neurobiologie, Max Planck Institut fur experimentelle Medizin, D 37075 Gottingen, Germany
    J Cell Sci 115:4399-411. 2002
    ..b>RasGRP1 (in Ras/Raf/MEK/ERK signalling) and Munc13-1 (in neurotransmitter secretion) are examples of non-PKC ..
  94. ncbi Transgenic expression of RasGRP1 induces the maturation of double-negative thymocytes and enhances the production of CD8 single-positive thymocytes
    Anne M Norment
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    J Immunol 170:1141-9. 2003
    b>RasGRP1 is a guanine nucleotide exchange factor for Ras that is required for the efficient production of both CD4 and CD8 single-positive thymocytes...
  95. ncbi T cell activation in vivo targets diacylglycerol kinase alpha to the membrane: a novel mechanism for Ras attenuation
    Miguel A Sanjuan
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Campus de Cantoblanco, Madrid, Spain
    J Immunol 170:2877-83. 2003
    ..translocation to the membrane correlates with rapid translocation of Ras guanyl nucleotide-releasing protein (RasGRP), a nucleotide exchange activator for Ras that associates to the membrane through a diacylglycerol-binding domain...
  96. ncbi Integration of DAG signaling systems mediated by PKC-dependent phosphorylation of RasGRP3
    Christine Teixeira
    Department of Biochemistry, University of Alberta, Edmonton, Canada
    Blood 102:1414-20. 2003
    Members of the RasGRP family of Ras activators have C1 domains that bind diacylglycerol (DAG) and DAG analogs such as the tumor-promoting phorbol esters...
  97. ncbi Exchange factors of the RasGRP family mediate Ras activation in the Golgi
    Maria J Caloca
    Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, University of Salamanca, Consejo Superior de Investigaciones Cientificas, Campus Unamuno, E 37007 Salamanca, Spain
    J Biol Chem 278:33465-73. 2003
    ....
  98. ncbi Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1
    Katrin Layer
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Immunity 19:243-55. 2003
    ..Positional mapping of the disease-associated locus revealed a lesion in Rasgrp1 that prevented the translation of the RasGRP1 protein...
  99. pmc Requirement for Ras guanine nucleotide releasing protein 3 in coupling phospholipase C-gamma2 to Ras in B cell receptor signaling
    Masatsugu Oh-hora
    Dept of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570 8506, Japan
    J Exp Med 198:1841-51. 2003
    ..Ras guanine nucleotide exchange factors, Son of sevenless (Sos) and Ras guanine nucleotide releasing protein (RasGRP), have been implicated in controlling Ras activation when cell surface receptors are stimulated...
  100. ncbi RasGRP1 sensitizes an immature B cell line to antigen receptor-induced apoptosis
    Benoit Guilbault
    Terry Fox Laboratory, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6, Canada
    J Biol Chem 279:19523-30. 2004
    b>RasGRP1 is a guanine nucleotide exchange factor that activates Ras GTPases and is activated downstream of antigen receptors on both T and B lymphocytes...
  101. ncbi Non-kinase second-messenger signaling: new pathways with new promise
    Gregory M Springett
    Developmental Chemotherapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Bioessays 26:730-8. 2004
    ..Exchange Factor) and CalDAG-GEF (Calcium and Diacylglycerol regulated Guanine nucleotide Exchange Factor) or RasGRP (Ras Guanine nucleotide Releasing Protein) are able to mediate some of the physiologic effects of the second ..

Research Grants25

  1. Novel Molecules in Calcium Signaling in Platelets
    Wolfgang Bergmeier; Fiscal Year: 2013
    ..An in-depth analysis of how CD-GEFI regulates platelet function in vitro and in vivo will aid in its establishment as a target for antiplatelet therapy. ..
  2. Mechanistic Studies of Ras-MAPK Signals: Specialzed Cues for the T cell Lineage?
    Jeroen Roose; Fiscal Year: 2011
    ..Our recent publications reported that RasGRP1 signals to Ras in an analog manner while SOS signals to Ras in a digital manner...
  3. Differential regulation of Ras nucleotide exchange factors
    JEFFREY SCOTT IWIG; Fiscal Year: 2012
    ..T-cell receptor activation can cause varying degrees of Ras stimulation through the combined action of two GEFs, RasGrp1 and SOS, which leads to cell proliferation or death, depending on the strength and duration of the extracellular ..
  4. NOVEL SECOND MESSENGER SIGNALING IN THE STRIATUM
    Ann M Graybiel; Fiscal Year: 2013
    ..The work proposed is highly significant for understanding signaling in key basal ganglia neurons whose function is essential for normal behavior and whose dysfunction leads to major extrapyramidal disorders. ..
  5. Arthur Weiss; Fiscal Year: 2016
    ..of LAT;and, (Project #2) the activation of Ras downstream of LAT by the guanine nucleotide exchange factors (GEFs) RasGRP and SOS...
  6. NOVEL SECOND MESSENGER SIGNALING IN THE STRIATUM
    ANN GRAYBIEL; Fiscal Year: 2003
    ..Understanding these novel second messenger signaling molecules will therefore bring insights to understanding fundamentally important brain functions and will help in elucidating brain disorders. ..
  7. JOE WILLIAM RAMOS; Fiscal Year: 2015
    ..Using the mouse skin model, we have identified RasGRP1 as a novel regulator of skin carcinogenesis...
  8. Compartment Specific Signaling of Ras
    MARK REID PHILIPS; Fiscal Year: 2010
    ..We mapped the pathway to activation on Golgi as one involving EGFR/PLC(/DAG + Ca++/RasGRP1. More recently we have discovered that in T lymphocytes, signaling through the antigen receptor (TCR) and the (2 ..
  9. Fine Mapping and Functional Evaluation of Selected Type 1 Diabetes Loci
    Hakon Hakonarson; Fiscal Year: 2009
    ..For genes with known function, such as IFIH1, PTPN22, RASGRP1, BACH2, UBASH3, this function will be compared, ex vivo, between cells from individuals of different genotypes...
  10. RasGRP4-dependent Responses in Mast Cells
    Richard Stevens; Fiscal Year: 2009
    ..recently cloned the cDNAs and genes that encode the fourth member of the Ras Guanine Nucleotide Releasing Protein (RasGRP) family of signaling proteins...
  11. Wolfgang Bergmeier; Fiscal Year: 2014
    ..The successful completion of this proposal will accelerate the rational design of novel therapeutics for immune-mediated platelet disorders. ..
  12. Ras activation pathways in UVR-induced epidermal transformation
    JOE WILLIAM RAMOS; Fiscal Year: 2013
    ..Studies from our lab have demonstrated a role for RasGRP1 in skin tumorigenesis through its ability to activate Ras, and support the concept that stimulation of RasGRP1 by ..
  13. DGK in T Cell Regulation and Tolerance
    Thomas F Gajewski; Fiscal Year: 2010
    ..increased expression of the transcriptional regulator EGR2, and we have identified EGR-farnily RasGRP-mediated Ras activation in the anergic state. peripheral I cells...
  14. XIAOPING ZHONG; Fiscal Year: 2016
    ..Using genetically manipulated mice and cell line models, we have recently revealed that the RasGRP1-Ras- Mek1/2-Erk1/2 pathway is critical for both mTORC1 and mTORC2 activation in T cells following T cell receptor ..
  15. Thomas F Gajewski; Fiscal Year: 2016
    ..expression of lipid kinases of the diacylglycerol kinase (DGK) family participate in the suppression of RasGRP-mediated Ras activation and contribute to T cell dysfunction in the anergic state...
  16. Andre Limnander; Fiscal Year: 2014
    ..b>RasGRP1-deficient mice have a substantial developmental block in T cell development that results in T cell lymphopenia, ..
  17. XIAOPING ZHONG; Fiscal Year: 2016
    ..expressed in T cells, negatively control T cell activation by inhibiting TCR-induced activation of the DAG-RasGRP1-Ras-Erk1/2-AP1 cascade...
  18. Regulation of tumor promotion by RasGRP1
    Patricia Lorenzo; Fiscal Year: 2002
    ..We have recently characterized the novel Ras activator RasGRP1 as a high affinity receptor for phorbol esters, and our preliminary data indicate that RasGRP1 is expressed in ..
  19. In Vivo Delivery of siRNAs as a Novel Approach to Inducing Mixed Chimerism
    Megan Sykes; Fiscal Year: 2010
    ..induced by the ICAM-1 construct-siRNA complex in vivo;and 3) Test the hypothesis that specific silencing of RasGRP1, cyclin D1, and bcl-xL in activated T cells is sufficient to tolerize donor-reactive T cells, permitting ..
  20. Role of CalDAG-GEFI in striatal function
    JILL CRITTENDEN; Fiscal Year: 2004
    ..In addition, I propose biochemical experiments to test whether CalDAG-GEFI interacts with members of the ERK cascade in the striatum and whether signaling through this cascade is disrupted in CalDAG-GEFI knockout mice. ..
  21. The small G protein Rap 1 in T cell activation/anergy
    PHILIP STORK; Fiscal Year: 2005
    ..In addition, we will test the hypothesis that CD28 co-stimulation achieves increased ERK activation, IL-2 production and proliferation by blocking Rap1 activation. ..
  22. HORMONAL REGULATION OF MAP KINASE VIA RAP1 AND B-RAF
    Philip J S Stork; Fiscal Year: 2010
    ..We will determine the biochemical basis for this specificity of Rap1 for B-Raf in Specific Aim 3. In this aim, we will also establish novel mouse models to test the hypothesis that B-Raf has irreplaceable functions in vivo. ..
  23. NEURONAL ACTIVITY AND INTRACELLULAR SIGNALING
    PHILIP STORK; Fiscal Year: 2003
    ..The applicant believes that the experiments outlined in this proposal may ultimately impact more general research on synaptic plasticity, long-term potentiation (LTP) and neuronal survival. ..
  24. Actin assembly in platelets & megakaryoctyes
    Charles Abrams; Fiscal Year: 2008
    ..In the second Aim, we will formally address how PIP2 drives reorganization of platelet actin using a combination of biochemistry, murine genetics, and ex vivo platelet adhesion models. ..
  25. Rheb GTPase as chemotherapeutic target for brain tumors
    LAWRENCE QUILLIAM; Fiscal Year: 2009
    ..They will address the molecular basis of non-Ras action of FTIs and demonstrate the value of targeting Rheb in cancer therapy. ..