rap1 gtp binding proteins

Summary

Summary: A genetically related subfamily of RAP GTP-BINDING PROTEINS that share homology with RAS PROTEINS. They bind to Ras effectors but do not activate them, therefore they may antagonize the effects of RAS PROTEINS. This enzyme was formerly listed as EC 3.6.1.47.

Top Publications

  1. ncbi A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
    Jorrit M Enserink
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Nat Cell Biol 4:901-6. 2002
  2. ncbi Rap1: a key regulator in cell-cell junction formation
    Matthijs R H Kooistra
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Cell Sci 120:17-22. 2007
  3. ncbi Spatio-temporal images of growth-factor-induced activation of Ras and Rap1
    N Mochizuki
    Department of Structural Analysis, National Cardiovascular Center Research Institute, 5 7 1 Fujishirodai, Suita Shi, Osaka 565 8565, Japan
    Nature 411:1065-8. 2001
  4. ncbi Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase
    Xavier Cullere
    Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Blood 105:1950-5. 2005
  5. ncbi RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1
    Koko Katagiri
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501 Japan
    Nat Immunol 4:741-8. 2003
  6. ncbi Epac1 regulates integrity of endothelial cell junctions through VE-cadherin
    Matthijs R H Kooistra
    Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center, Utrecht, The Netherlands
    FEBS Lett 579:4966-72. 2005
  7. ncbi RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion
    Esther M Lafuente
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 7:585-95. 2004
  8. ncbi PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2
    J de Rooij
    Laboratory for Physiological Chemistry, Center for Biomedical Genetics, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 274:38125-30. 1999
  9. ncbi Cellular functions of the Rap1 GTP-binding protein: a pattern emerges
    Emmanuelle Caron
    Department of Biological Sciences, The Flowers Building, Room 2 41, Armstrong Road, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK
    J Cell Sci 116:435-40. 2003
  10. ncbi Rap1 signalling: adhering to new models
    J L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nat Rev Mol Cell Biol 2:369-77. 2001

Research Grants

  1. The small G protein Rap 1 in T cell activation/anergy
    PHILIP STORK; Fiscal Year: 2005
  2. HORMONAL REGULATION OF MAP KINASE VIA RAP1 AND B-RAF
    Philip J S Stork; Fiscal Year: 2010
  3. NEURONAL ACTIVITY AND INTRACELLULAR SIGNALING
    PHILIP STORK; Fiscal Year: 2003
  4. Immunoreceptors
    Michael Dustin; Fiscal Year: 2008
  5. Validating microRNA Analysis in Human Postmortem Brain
    Yogesh Dwivedi; Fiscal Year: 2008
  6. Signal Transduction Mechanisms in Suicide Brain
    Yogesh Dwivedi; Fiscal Year: 2008
  7. MACROPHAGES, DENDRITIC CELLS AND PATHOGENS
    Carl Nathan; Fiscal Year: 2007
  8. Dihydrolipoamide Acyltransferase:Target for Chemotherapy
    Carl Nathan; Fiscal Year: 2004
  9. MYCOBACTERIAL RESISTANCE TO REACTIVE NITROGEN/OXYGEN
    Carl Nathan; Fiscal Year: 2003
  10. ROLE OF NO SYNTHASE-2 IN MURINE ALZHEIMER'S DISEASE
    Carl Nathan; Fiscal Year: 2004

Detail Information

Publications193 found, 100 shown here

  1. ncbi A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
    Jorrit M Enserink
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Nat Cell Biol 4:901-6. 2002
    ..Moreover, in cell lines in which cAMP activates ERK, inhibition of PKA and Ras, but not Rap1, abolished cAMP-mediated ERK activation. We conclude that cAMP-induced regulation of ERK and activation of Rap1 are independent processes...
  2. ncbi Rap1: a key regulator in cell-cell junction formation
    Matthijs R H Kooistra
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Cell Sci 120:17-22. 2007
    ..These findings point to a role of Rap1 in spatial and temporal control of cell-cell junction formation...
  3. ncbi Spatio-temporal images of growth-factor-induced activation of Ras and Rap1
    N Mochizuki
    Department of Structural Analysis, National Cardiovascular Center Research Institute, 5 7 1 Fujishirodai, Suita Shi, Osaka 565 8565, Japan
    Nature 411:1065-8. 2001
    ..These observations may resolve long-standing questions as to how Ras and Rap1 induce different cellular responses and how the signals for differentiation and survival are distinguished by neuronal cells...
  4. ncbi Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase
    Xavier Cullere
    Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Blood 105:1950-5. 2005
    ..Thus, Epac/Rap activation represents a new pathway for regulating endothelial cell barrier function...
  5. ncbi RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1
    Koko Katagiri
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501 Japan
    Nat Immunol 4:741-8. 2003
    ..Triggered by activated Rap1, RAPL associated with LFA-1 and rapidly relocated to the leading edge and accumulated at immunological synapses. Thus, RAPL regulates lymphocyte adhesion through the spatial distribution of LFA-1...
  6. ncbi Epac1 regulates integrity of endothelial cell junctions through VE-cadherin
    Matthijs R H Kooistra
    Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center, Utrecht, The Netherlands
    FEBS Lett 579:4966-72. 2005
    ..From these results we conclude that in human umbilical vein endothelial cells Epac1 controls VE-cadherin-mediated cell junction formation and induces reorganization of the actin cytoskeleton...
  7. ncbi RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion
    Esther M Lafuente
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 7:585-95. 2004
    ..RIAM knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion. Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin dynamics...
  8. ncbi PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2
    J de Rooij
    Laboratory for Physiological Chemistry, Center for Biomedical Genetics, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 274:38125-30. 1999
    ..This is the first example of an exchange factor acting on Rap2. We conclude that PDZ-GEF1 is a guanine nucleotide exchange factor, specific for Rap1 and Rap2, that is controlled by a negative regulatory domain...
  9. ncbi Cellular functions of the Rap1 GTP-binding protein: a pattern emerges
    Emmanuelle Caron
    Department of Biological Sciences, The Flowers Building, Room 2 41, Armstrong Road, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK
    J Cell Sci 116:435-40. 2003
    ....
  10. ncbi Rap1 signalling: adhering to new models
    J L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nat Rev Mol Cell Biol 2:369-77. 2001
    ....
  11. pmc MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of vascular endothelial cadherin-mediated cell adhesion
    Atsuko Sakurai
    Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka 565 8565, Japan
    Mol Biol Cell 17:966-76. 2006
    ..In addition, once activated, Rap1 upon cell-cell contacts positively regulate the adherens junction formation by relocating vinculin that supports VE-cadherin-based cell adhesion...
  12. ncbi Involvement of the c-Src-Crk-C3G-Rap1 signaling in the nectin-induced activation of Cdc42 and formation of adherens junctions
    Taihei Fukuyama
    Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine Faculty of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    J Biol Chem 280:815-25. 2005
    ..These results indicate that Rap1 is activated by nectins through the c-Src-Crk-C3G signaling and involved in the nectin-induced, c-Src- and FRG-mediated activation of Cdc42 and formation of AJs...
  13. ncbi Recognizing and defining true Ras binding domains I: biochemical analysis
    Sabine Wohlgemuth
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Otto Hahn Str 11, Dortmund 44227, Germany
    J Mol Biol 348:741-58. 2005
    ..These residues are important to qualify an RA/RB domain as a true candidate Ras or Rap effector...
  14. ncbi Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion
    Koko Katagiri
    Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Osaka 570 8506, Japan
    Nat Immunol 7:919-28. 2006
    ..Our study demonstrates a previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce cell polarity and adhesion of lymphocytes...
  15. pmc Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins
    Yu Li
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202, USA
    J Immunol 179:8322-31. 2007
    ....
  16. ncbi Activity-dependent dendritic spine structural plasticity is regulated by small GTPase Rap1 and its target AF-6
    Zhong Xie
    Department of Physiology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, Illinois 60611
    Neuron 48:605-18. 2005
    ..These results identify a signaling pathway that regulates activity-dependent synaptic structural plasticity and coordinates it with functional plasticity...
  17. ncbi Rap1 GTPase: functions, regulation, and malignancy
    Masakazu Hattori
    Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501
    J Biochem 134:479-84. 2003
    ..Recent extensive research has begun to unveil the roles of this controversial small G protein in physiology and diseases...
  18. ncbi RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans
    Y Liao
    Department of Physiology II, Kobe University School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    J Biol Chem 274:37815-20. 1999
    ..On the other hand, Ce-RA-GEF associated with and stimulated GDP/GTP exchange of both Ras and Rap1A. These results indicate that Ce-RA-GEF and Hs-RA-GEF define a novel class of Rap1A GEF molecules, which are conserved through evolution...
  19. ncbi The small GTPase Rap1 is required for Mn(2+)- and antibody-induced LFA-1- and VLA-4-mediated cell adhesion
    Kim M T de Bruyn
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Utrecht University, Universiteitsweg 100, P O Box 85060, 3508 AB Utrecht, The Netherlands
    J Biol Chem 277:29468-76. 2002
    ..We suggest that Rap1 determines the functional availability of integrins for productive binding to integrin ligands...
  20. pmc KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions
    Angela Glading
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 179:247-54. 2007
    ..Thus, Rap1 increases KRIT-1 targeting to endothelial cell-cell junctions where it suppresses stress fibers and stabilizes junctional integrity...
  21. pmc Cyclic AMP induces integrin-mediated cell adhesion through Epac and Rap1 upon stimulation of the beta 2-adrenergic receptor
    Savithri Rangarajan
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Netherlands
    J Cell Biol 160:487-93. 2003
    ..From these results we conclude that cAMP mediates receptor-induced integrin-mediated cell adhesion to fibronectin through the Epac-Rap1 signaling pathway...
  22. pmc Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion
    Marlena Duchniewicz
    Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D 14195 Berlin, Germany
    Mol Cell Biol 26:643-53. 2006
    ..Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins...
  23. pmc E-cadherin dis-engagement activates the Rap1 GTPase
    Sirisha Asuri
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Oncology Center, Indianapolis, Indiana 46202, USA
    J Cell Biochem 105:1027-37. 2008
    ..We hereby show that Rap1 plays a role in the maintenance and repair of E-cadherin junctions and is activated via an "outside-in" signaling pathway initiated by E-cadherin and mediated at least in part by PDZ-GEF I...
  24. ncbi Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs
    J de Rooij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 275:20829-36. 2000
    ..Epac1 becomes activated by a release of this inhibition when cAMP is bound...
  25. ncbi Prediction and validation of the distinct dynamics of transient and sustained ERK activation
    Satoru Sasagawa
    Undergraduate Program for Bioinformatics and Systems Biology, Graduate School of Information Science and Technology, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Nat Cell Biol 7:365-73. 2005
    ..Therefore, the Ras and Rap1 systems capture the temporal rate and concentration of growth factors, and encode these distinct physical properties into transient and sustained ERK activation, respectively...
  26. ncbi Evidence for a role for the Dictyostelium Rap1 in cell viability and the response to osmotic stress
    Rujun Kang
    Department of Microbiology and Immunology, University of British Columbia, 300 6174 University Blvd, Vancouver, BC V6T 1Z3, Canada
    J Cell Sci 115:3675-82. 2002
    ..Rap1 was also activated in response to low temperature but not in response to low osmolarity or high temperature...
  27. ncbi Rap1 activation in response to cAMP occurs downstream of ras activation during Dictyostelium aggregation
    Parvin Bolourani
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 283:10232-40. 2008
    ..The finding that in vitro guanylyl cyclase activation is also abolished in the rasC(-)/rasG(-)/[act15]:carA strain identifies RasG/RasC as the presumptive monomeric GTPases required for this activation...
  28. pmc Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion
    Trever G Bivona
    Deparment of Cell Biology, New York University School of Medicine, 550 First Ave, New York, NY 10016, USA
    J Cell Biol 164:461-70. 2004
    ..These observations may explain some of the biological differences between these GTPases...
  29. pmc Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of chemotaxing cells
    Taeck J Jeon
    Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 179:833-43. 2007
    ..We suggest that RapGAP1 functions in the spatial and temporal regulation of attachment sites through MyoII assembly via regulation of Rap1-guanosine triphosphate...
  30. ncbi A third-generation bisphosphonate, minodronic acid (YM529), augments the interferon alpha/beta-mediated inhibition of renal cell cancer cell growth both in vitro and in vivo
    Takeshi Yuasa
    Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara cho Shogoin, Sakyo ku, Kyoto 606 8507, Japan
    Clin Cancer Res 11:853-9. 2005
    ..Minodronic acid (YM529) is a third-generation nitrogen-containing bisphosphonate. Here, we have investigated the therapeutic efficacy of YM529 against renal cell cancer (RCC) alone or in combination with IFN both in vitro and in vivo...
  31. ncbi RA-GEF-1, a guanine nucleotide exchange factor for Rap1, is activated by translocation induced by association with Rap1*GTP and enhances Rap1-dependent B-Raf activation
    Y Liao
    Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    J Biol Chem 276:28478-83. 2001
    ....
  32. 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
    ..These results suggest that analogous signaling defects are likely to occur in the central nervous system when CalDAG-GEFI is absent or compromised in function...
  33. ncbi The Rap GTPases regulate B cell migration toward the chemokine stromal cell-derived factor-1 (CXCL12): potential role for Rap2 in promoting B cell migration
    Sarah J McLeod
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
    J Immunol 169:1365-71. 2002
    ..Conversely, expressing a constitutively active form of Rap2 increased SDF-1-induced B cell migration. Thus, the Rap GTPases control cellular processes that are important for B cells to migrate toward SDF-1...
  34. 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...
  35. pmc Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues
    Tatsuo Kinashi
    Department of Molecular Genetics, Graduate School of Medicine, Institute of Live Research, Kansai Medical School, Osaka, Japan
    Immunology 116:164-71. 2005
    ..Targeted deletion of RAPL in mice has demonstrated multiple indispensable roles for this protein in lymphocyte and dendritic cell trafficking critical for immunosurveillance...
  36. pmc RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences
    Ho Sup Lee
    Department of Medicine, University of California San Diego, La Jolla, California 92093 0726, USA
    J Biol Chem 284:5119-27. 2009
    ..These data establish the mechanism whereby MRL proteins interact with both talin and Ras GTPases to activate integrins...
  37. ncbi Regulation of lymphocyte adhesion and migration by the small GTPase Rap1 and its effector molecule, RAPL
    Tatsuo Kinashi
    Bayer chair Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Immunol Lett 93:1-5. 2004
    ..The linkage between cell polarization and integrin activation through Rap1/RAPL signaling likely provides immune cells with their dynamic trafficking capability...
  38. ncbi Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling
    Eric Sebzda
    Lymphocyte Activation Laboratory, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Immunol 3:251-8. 2002
    ..This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation...
  39. ncbi Linking Rap to cell adhesion
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, UMC Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Curr Opin Cell Biol 17:123-8. 2005
    ..Recently, several effector proteins for Rap1 have been identified providing a clear link between Rap1 and actin dynamics. Furthermore, evidence is accumulating that Rap1 functions in the spatial and temporal control of cell polarity...
  40. pmc Rap1 regulates the formation of E-cadherin-based cell-cell contacts
    Catherine Hogan
    MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London WC1E 6BT, United Kingdom
    Mol Cell Biol 24:6690-700. 2004
    ..Furthermore, our data suggest that Cdc42 functions downstream of Rap1 in this process. We conclude that Rap1 plays a vital role in the establishment of E-cadherin-based cell-cell adhesion...
  41. ncbi Nerve growth factor activates persistent Rap1 signaling in endosomes
    C Wu
    Departments of Neurology and Neurological Sciences and of Pediatrics and the Program in Neuroscience, Stanford University School of Medicine, Stanford, California 94305, USA
    J Neurosci 21:5406-16. 2001
    ..We propose that endosomes are a site from which NGF induces the prolonged activation of Rap1 and MAPK...
  42. ncbi The role of Rap1 in integrin-mediated cell adhesion
    J L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochem Soc Trans 31:83-6. 2003
    ..From these results, we conclude that one of the functions of receptor-induced Rap1 activation is inside-out regulation of integrins...
  43. ncbi E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function
    Fiorella Balzac
    Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5 bis, Torino, 10126, Italy
    J Cell Sci 118:4765-83. 2005
    ..Our findings provide the first evidence of an E-cadherin-modulated endosomal signaling pathway involving Rap1, and suggest that cadherins may have a novel modulatory role in integrin adhesive functions by fine-tuning Rap1 activation...
  44. ncbi Integrin avidity regulation: are changes in affinity and conformation underemphasized?
    Christopher V Carman
    Center for Blood Research, Harvard Medical School, Department of Pathology, 200 Longwood Avenue, Boston, MA 02115, USA
    Curr Opin Cell Biol 15:547-56. 2003
    ..Recent advances have shed light on the structural basis for affinity regulation and on the signaling mechanisms responsible for both affinity and valency modes of regulation...
  45. ncbi Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn
    Takashi Hoshino
    Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine Faculty of Medicine, Osaka 565 0871, Japan
    J Biol Chem 280:24095-103. 2005
    ....
  46. ncbi Epac/Rap1 pathway regulates microvascular hyperpermeability induced by PAF in rat mesentery
    R H Adamson
    Physiology and Membrane Biology, School of Medicine, University of California at Davis, Davis, CA 95616, USA
    Am J Physiol Heart Circ Physiol 294:H1188-96. 2008
    ..Our results indicate that increased permeability in intact microvessels by acute inflammatory agents such as PAF is the result of the decreased effectiveness of the Epac/Rap1 pathway modulation of cell-cell adhesion...
  47. pmc Mechanism of the spatio-temporal regulation of Ras and Rap1
    Yusuke Ohba
    Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871, Japan
    EMBO J 22:859-69. 2003
    ..Thus we propose that GAP primarily dictates the spatial regulation of Ras family G proteins, whereas GEF primarily determines the timing of Ras activation...
  48. ncbi Does Rap1 deserve a bad Rap?
    Philip J S Stork
    Vollum Institute, L474 Oregon Health Sciences University, Portland 97201, USA
    Trends Biochem Sci 28:267-75. 2003
    ..These diverse functions of Rap1 underscore that the activation and action of Rap1 are regulated by complex factors that are cell-type specific...
  49. pmc RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activation
    Gael Menasche
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 415 BRBII III, 421 Curie Blvd, Philadelphia, PA 19104 6160, USA
    Mol Cell Biol 27:4070-81. 2007
    ..These results describe for the first time a link between ADAP/SKAP-55 and the Rap1/RIAM complex and provide a potential new mechanism for TCR-mediated integrin activation...
  50. pmc Rap1 functions as a key regulator of T-cell and antigen-presenting cell interactions and modulates T-cell responses
    Koko Katagiri
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Mol Cell Biol 22:1001-15. 2002
    ..Moreover, constitutive Rap1 activation rendered T cells unresponsive with accumulation of p27(Kip1). Our study indicates that the activation state of Rap1 has a decisive effect on the T-cell response to antigen...
  51. ncbi Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy
    Coskun Ulucan
    Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan
    Am J Physiol Heart Circ Physiol 293:H1662-72. 2007
    ..Furthermore, our results suggest the importance of the stoichiometry of Epac over that of Rap in cellular biological effects...
  52. pmc Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors
    William T Arthur
    Fred Hutchison Cancer Research Center, Seattle, WA 98109, USA
    J Cell Biol 167:111-22. 2004
    ..These results lead us to propose that Rap1 promotes cell spreading by localizing a subset of Rac GEFs to sites of active lamellipodia extension...
  53. ncbi Protein kinase D1 and the beta 1 integrin cytoplasmic domain control beta 1 integrin function via regulation of Rap1 activation
    Ricardo B Medeiros
    Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, 55455, USA
    Immunity 23:213-26. 2005
    ..Therefore, PKD1 promotes integrin activation in T cells by regulating Rap1 activation and membrane translocation via interactions with the beta1 integrin subunit cytoplasmic domain...
  54. pmc Regulation of Rap1 activity is required for differential adhesion, cell-type patterning and morphogenesis in Dictyostelium
    Katie Parkinson
    Faculty of Life Sciences, University of Manchester, Michael Smith Building, Manchester, UK
    J Cell Sci 122:335-44. 2009
    ..Finally, we show that inactivation of RapGAPB affects prestalk and prespore cell adhesion. We therefore propose that a possible mechanism for RapGAPB-regulated cell sorting is through differential adhesion...
  55. ncbi Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3
    Jaewon Han
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Curr Biol 16:1796-806. 2006
    ..Many different signaling molecules that regulate integrin affinity have been described, but a pathway that connects agonist stimulation to talin binding and activation has not been mapped...
  56. ncbi The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin
    Jorrit M Enserink
    Biotechnology Centre of Oslo, University of Oslo, Blindern, N 0317 Oslo, Norway
    J Biol Chem 279:44889-96. 2004
    ..They also define different roles for the laminin-binding integrins in regulated cell adhesion and subsequent cell spreading...
  57. ncbi Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes
    Hisakazu Fujita
    Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka 565 8565, Japan
    J Biol Chem 280:5022-31. 2005
    ..Collectively, the locally activated Rap1 and its association with RAPL controls the directional migration of vascular endothelial cells...
  58. ncbi Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b
    Wenying Zhang
    La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 278:23978-83. 2003
    ..Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells...
  59. pmc Negative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase
    Yuan Shao
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    EMBO Rep 4:425-31. 2003
    ..Thus, Cbl negatively regulates Rap1 activation, probably through a proteolysis-independent E3-ubiquitin-ligase activity of Cbl that modulates protein-protein interactions...
  60. ncbi The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane
    Yu Li
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, and Walther Cancer Institute, Indianapolis, Indiana 46202, USA
    J Biol Chem 281:2506-14. 2006
    ..Therefore, despite its previous description as a Ras antagonist or independently functioning GTPase, Rap1/Krev-1 may additionally act downstream of Ras in cells that express the cyclic AMP-regulated GEF, Epac2...
  61. ncbi AF6 negatively regulates Rap1-induced cell adhesion
    Zhongchun Zhang
    Department of Physiological Chemistry and Centre of Biomedical Genetics, University Medical Centre, Utrecht 3508 AB, The Netherlands
    J Biol Chem 280:33200-5. 2005
    ..Thus, AF6 may buffer RapGTP in resting T cells and maintain them in a non-adherent state...
  62. ncbi Insight into catalysis of a unique GTPase reaction by a combined biochemical and FTIR approach
    Partha P Chakrabarti
    Abteilung Strukturelle Biologie, Max Planck Institut fur molekulare Physiologie, D 44227 Dortmund, Germany
    J Mol Biol 367:983-95. 2007
    ....
  63. ncbi Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory
    Alexei Morozov
    Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, 1051 Riverside Drive, New York, NY 10032, USA
    Neuron 39:309-25. 2003
    ..These results indicate that Rap1 couples cAMP signaling to a selective membrane-associated pool of p42/44MAPK to control excitability of pyramidal cells, the early and late phases of LTP, and the storage of spatial memory...
  64. pmc Rap1 controls cell adhesion and cell motility through the regulation of myosin II
    Taeck J Jeon
    Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 176:1021-33. 2007
    ..We suggest that Rap1/Phg2 plays a role in controlling leading edge myosin II disassembly while passively allowing myosin II assembly along the lateral sides and posterior of the cell...
  65. pmc The AF-6 homolog canoe acts as a Rap1 effector during dorsal closure of the Drosophila embryo
    Benjamin Boettner
    Laboratory of Developmental Neurogenetics, Rockefeller University, New York, New York 10021, USA
    Genetics 165:159-69. 2003
    ..We further show that Rap1 acts upstream of Cno, but that Rap1, unlike Cno, is not involved in the stimulation of JNK pathway activity, indicating that Cno has both a Rap1-dependent and a Rap1-independent function in the DC process...
  66. ncbi Characterization of the GbpD-activated Rap1 pathway regulating adhesion and cell polarity in Dictyostelium discoideum
    Arjan Kortholt
    Department of Molecular Cell Biology, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands
    J Biol Chem 281:23367-76. 2006
    ..Phg2, a serine/threonine-specific kinase, directly interacts with Rap1 via its Ras association domain...
  67. ncbi Rap1 regulates E-cadherin-mediated cell-cell adhesion
    Leo S Price
    Department of Physiological Chemistry and the Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 279:35127-32. 2004
    ..Our results imply that Rap may function in a broader manner to regulate the function of cell-surface adhesion receptors...
  68. ncbi The GTPase-activating protein Rap1GAP uses a catalytic asparagine
    Oliver Daumke
    Max Planck Institut fur molekulare Physiologie, Otto Hahnstr 11, 44227 Dortmund, Germany
    Nature 429:197-201. 2004
    ..9 A. By mutational analysis, fluorescence titration and stopped-flow kinetic assay, we demonstrate that Rap1GAP provides a catalytic asparagine to stimulate GTP hydrolysis. Implications for the disease tuberous sclerosis are discussed...
  69. ncbi Rap1: a turnabout for the crosstalk between cadherins and integrins
    Saverio Francesco Retta
    Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5 bis, I 10126 Torino, Italy
    Eur J Cell Biol 85:283-93. 2006
    ..In particular, it highlights some of the novel results recently obtained that raise the possibility of a pivotal role for Rap1 in the functional crosstalk between cadherins and integrins, suggesting interesting new regulatory mechanisms...
  70. ncbi RAPL: taking the Rap in immunity
    Leo S Price
    Nat Immunol 5:1007-8. 2004
  71. ncbi Vascular endothelial cadherin-mediated cell-cell adhesion regulated by a small GTPase, Rap1
    Shigetomo Fukuhra
    Department of Structural Analysis, National Cardiovascular Center Research Institute, 5 7 1 Fujishirodai, Suita, Osaka 565 8565, Japan
    J Biochem Mol Biol 39:132-9. 2006
    ..A further analysis of the VE-cadherin recycling system will aid the understanding of cell adhesion/deadhesion mechanisms mediated by VE-cadherin in response to extracellular stimuli during development and angiogenesis...
  72. pmc Down-regulation of Rap1 activity is involved in ephrinB1-induced cell contraction
    Jurgen A Riedl
    Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochem J 389:465-9. 2005
    ..From these results, we conclude that down-regulation of Rap1 is a prerequisite for ephrin-induced cell retraction in colon cells...
  73. ncbi F-actin-dependent translocation of the Rap1 GDP/GTP exchange factor RasGRP2
    Mariía J Caloca
    Centro de Investigacion del Cancer, University of Salamanca Consejo Superior de Investigaciones Cientiíficas, Campus Unamuno, E 37007 Salamanca, Spain
    J Biol Chem 279:20435-46. 2004
    ..These results reveal a novel function of the actin cytoskeleton in mediating the spatial activation of Ras subfamily GTPases through the selective recruitment of GDP/GTP exchange factors...
  74. pmc The critical cytoplasmic regions of the alphaL/beta2 integrin in Rap1-induced adhesion and migration
    Yumi Tohyama
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Japan
    Mol Biol Cell 14:2570-82. 2003
    ..Our study revealed novel requirements of amino acid residues of the LFA-1 cytoplasmic region in the response to the inside-out signaling and the subsequent deadhesion process...
  75. ncbi Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction
    J F Rebhun
    Department of Biochemistry and Molecular Biology and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 275:34901-8. 2000
    ..In addition, a constitutively active M-Ras(71L) mutant inhibited the ability of MR-GEF to promote Rap1A activation in a dose-dependent manner. These data suggest that M-Ras may inhibit Rap1 in order to elicit its biological effects...
  76. ncbi Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of beta1 integrin-mediated hematopoietic cell adhesion
    A Arai
    Department of Hematology and Oncology and the Department of Bioregulatory Medicine and Rheumatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo 113, Japan
    J Biol Chem 276:10453-62. 2001
    ....
  77. pmc Drosophila PDZ-GEF, a guanine nucleotide exchange factor for Rap1 GTPase, reveals a novel upstream regulatory mechanism in the mitogen-activated protein kinase signaling pathway
    Jun Hee Lee
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305 701, Korea
    Mol Cell Biol 22:7658-66. 2002
    ..Collectively, our findings identify dPDZ-GEF as a novel upstream regulator of various morphogenetic pathways and demonstrate the presence of a novel, Ras-independent mechanism for activating the MAP kinase signaling pathway...
  78. pmc Coordinated regulation of Rap1 and thyroid differentiation by cyclic AMP and protein kinase A
    O M Tsygankova
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA
    Mol Cell Biol 21:1921-9. 2001
    ..These findings reveal complex regulation of Rap1 by cAMP including PKA-independent activation and PKA-dependent negative feedback regulation. Both signals appear to be required for TSH signaling to Akt...
  79. ncbi Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by rif proteins
    K Mishra
    Department of Molecular Biology University of Geneva 30 quai Ernest Ansermet, Geneva 4, Switzerland CH 1211
    Curr Biol 9:1123-6. 1999
    ..Our data implicate a role for Ku in the competition between Sir and Rif proteins for access to the telomeric array of Rap1p molecules, which results in a balance between telomeric silencing and telomere length control...
  80. pmc Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis
    Y Ohba
    Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871, Japan
    EMBO J 20:3333-41. 2001
    ..In conclusion, C3G-dependent activation of Rap1 is required for adhesion and spreading of embryonic fibroblasts and for the early embryogenesis of the mouse...
  81. ncbi Rap1 GTPase regulation of adherens junction positioning and cell adhesion
    Andrea L Knox
    Wellcome CRC Institute and Department of Anatomy, University of Cambridge, Cambridge CB2 1QR, UK
    Science 295:1285-8. 2002
    ..Rap1 is enriched at adherens junctions, particularly between newly divided sister cells where it may reseal the adherens junction ring. The regulation of adherens junction positioning could play a role in cell mobility and cell division...
  82. ncbi Rap-specific GTPase activating protein follows an alternative mechanism
    Thilo Brinkmann
    Max Planck Institut fur molekulare Physiologie, Otto Hahn Strasse 11, 44227 Dortmund, Germany
    J Biol Chem 277:12525-31. 2002
    ..As an alternative, Rap1(F64A) is shown by kinetic and cell biological studies to be a Rap1GAP-resistant mutant. This study supports the notion of a completely different mechanism of the Rap1GAP-catalyzed GTP-hydrolysis reaction on Rap1...
  83. ncbi Differential signaling of cyclic AMP: opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B activation
    Fang C Mei
    Department of Pharmacology, School of Medicine, The University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 277:11497-504. 2002
    ..It is proposed that the net outcome of cAMP signaling is dependent upon the dynamic abundance and distribution of intracellular Epac and PKA...
  84. pmc The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin
    B Boettner
    Cold Spring Harbor Laboratories, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Proc Natl Acad Sci U S A 97:9064-9. 2000
    ..To our knowledge, AF-6 is the only integral component in cell-cell junctions discovered thus far that interacts with profilin and thus could modulate actin modeling proximal to adhesion complexes...
  85. ncbi AF-6 controls integrin-mediated cell adhesion by regulating Rap1 activation through the specific recruitment of Rap1GTP and SPA-1
    Li Su
    Department of Immunology and Cell Biology, Graduate School of Medicine and Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 278:15232-8. 2003
    ..These results suggested that AF-6 could control integrin-mediated cell adhesion by regulating Rap1 activation through the recruitment of both SPA-1 and Rap1GTP via distinct domains...
  86. ncbi Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors
    Willem Jan Pannekoek
    Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochim Biophys Acta 1788:790-6. 2009
    ..In this review, we will highlight the latest findings on the Rap signaling network in the control of epithelial and endothelial cell-cell junctions...
  87. ncbi Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway-mediated Rap1 activation
    Akira Sakakibara
    Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187 8502, Japan
    J Cell Sci 115:4915-24. 2002
    ..Moreover, expression of Myr-Chat enhanced integrin-mediated cell adhesion. Taken together we propose a novel role for the Chat-Cas complex in controlling cell adhesion via the activation of Rap1...
  88. ncbi Crosstalk between Rap1 and Rac regulates secretion of sAPPalpha
    Marjorie Maillet
    Cardiologie Cellulaire et Moléculaire, INSERM U 446, Universite Paris Sud, Faculte de Pharmacie, F 92296 Chatenay Malabry, France
    Nat Cell Biol 5:633-9. 2003
    ..Our data identify an unsuspected connection between two families of small GTPases and imply that Rac can function downstream of cAMP/Epac1/Rap1 in a novel signal transduction secretory pathway...
  89. pmc Rap1 activation in collagen phagocytosis is dependent on nonmuscle myosin II-A
    Pamela D Arora
    CIHR Group in Matrix Dynamics, University of Toronto, Toronto, ON M5S 3E2, Canada
    Mol Biol Cell 19:5032-46. 2008
    ..We conclude that MLC phosphorylation in response to initial collagen-bead binding promotes NM II-A filament assembly; binding of Rap1 to myosin filaments enables Rap1-dependent integrin activation and enhanced collagen phagocytosis...
  90. ncbi PKA phosphorylation of Src mediates Rap1 activation in NGF and cAMP signaling in PC12 cells
    Yutaro Obara
    The Vollum Institute, L474, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    J Cell Sci 117:6085-94. 2004
    ..PKA phosphorylation of Src may therefore be required for Rap1 activation in PC12 cells...
  91. pmc Tissue inhibitor of metalloproteinase-2 promotes neuronal differentiation by acting as an anti-mitogenic signal
    Leonor Perez-Martinez
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
    J Neurosci 25:4917-29. 2005
    ....
  92. ncbi Thyrotropin activates mitogen-activated protein kinase pathway in FRTL-5 by a cAMP-dependent protein kinase A-independent mechanism
    L Iacovelli
    Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy
    Mol Pharmacol 60:924-33. 2001
    ..This novel mechanism could integrate other pathways involved in TSH-stimulated proliferative response...
  93. ncbi Epac1-mediated Rap1 activation is not required for the production of nitric oxide in BV2, murine microglial cells
    Eun Yi Moon
    Laboratory of Human Genomics, Korea Research Institute of Bioscience and Biotechnology KRIBB, Taejeon, Korea
    J Neurosci Res 81:38-44. 2005
    ..This suggests that LPS-stimulated NO production is mainly PKA-dependent and also that Epac1-mediated Rap1 activation is not required for the induction of NO production...
  94. ncbi The cyclic AMP-Epac1-Rap1 pathway is dissociated from regulation of effector functions in monocytes but acquires immunoregulatory function in mature macrophages
    Tone Bryn
    Biotechnology Centre of Oslo, University of Oslo, Norway
    J Immunol 176:7361-70. 2006
    ..In conclusion, the Epac1-Rap1 pathway is present in both monocytes and macrophages, but only regulates specific immune effector functions in macrophages...
  95. ncbi Elevation of cyclic AMP in Jurkat T-cells provokes distinct transcriptional responses through the protein kinase A (PKA) and exchange protein activated by cyclic AMP (EPAC) pathways
    Suzanne Fuld
    Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Davidson Building, Glasgow G12 8QQ, Scotland, UK
    Exp Cell Res 309:161-73. 2005
    ..The control of gene expression by cyclic AMP in Jurkat T-cells therefore requires input from the EPAC signalling cascade...
  96. ncbi CXCL13 is an arrest chemokine for B cells in high endothelial venules
    Naotoshi Kanemitsu
    Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine C8, 2 2, Yamada oka, Suita, 565 0871, Japan
    Blood 106:2613-8. 2005
    ..These data identify CXCL13 as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an important role in B-cell entry into not only PPs but also MLNs...
  97. ncbi Cyclic adenosine 5'-monophosphate-stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and protein kinase A signaling pathways
    Jing Li
    Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555 0536, USA
    Mol Endocrinol 21:159-71. 2007
    ..Moreover, PGE2, a potent mediator of inflammation and associated with colorectal carcinogenesis, stimulates NT release suggesting a possible link between PGE2 and NT on intestinal inflammatory disorders and colorectal cancers...
  98. pmc Soluble adenylyl cyclase mediates nerve growth factor-induced activation of Rap1
    Alexander M Stessin
    Department of Pharmacology, and Tri institutional M D Ph D Program, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 281:17253-8. 2006
    ..These results identify sAC as a mediator of NGF signaling and reveal the existence of distinct pathways leading to cAMP-dependent signal transduction...
  99. pmc Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and together with Rap1b controls human endothelial cell functions
    Jingliang Yan
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Mol Cell Biol 28:5803-10. 2008
    ..These observations place Rap1 centrally in the human angiogenic process and suggest that both the Rap1a and Rap1b proteins are required for angiogenesis and that Rap1 is a critical mediator of FGF-induced ERK activation...
  100. ncbi Enhanced functional gap junction neoformation by protein kinase A-dependent and Epac-dependent signals downstream of cAMP in cardiac myocytes
    Satoshi Somekawa
    Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka, Japan
    Circ Res 97:655-62. 2005
    ..Collectively, PKA and Epac cooperatively enhance functional GJ neoformation in cardiomyocytes...
  101. ncbi Coordinate regulation of forskolin-induced cellular proliferation in macrophages by protein kinase A/cAMP-response element-binding protein (CREB) and Epac1-Rap1 signaling: effects of silencing CREB gene expression on Akt activation
    Uma K Misra
    Department of Pathology, Duke University, Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:38276-89. 2005
    ..We conclude that forskolin mediates cellular proliferation via cAMP-dependent activation of both PKA and Epac...

Research Grants21

  1. 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. ..
  2. 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. ..
  3. 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. ..
  4. Immunoreceptors
    Michael Dustin; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  5. Validating microRNA Analysis in Human Postmortem Brain
    Yogesh Dwivedi; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  6. Signal Transduction Mechanisms in Suicide Brain
    Yogesh Dwivedi; Fiscal Year: 2008
    ..abstract_text> ..
  7. MACROPHAGES, DENDRITIC CELLS AND PATHOGENS
    Carl Nathan; Fiscal Year: 2007
    ..Cores provide for BSL3 wet lab and mouse work; microarray analysis of gene expression; computation and comparison of gene expression results; and high throughput screening of chemical libraries. ..
  8. Dihydrolipoamide Acyltransferase:Target for Chemotherapy
    Carl Nathan; Fiscal Year: 2004
    ..abstract_text> ..
  9. MYCOBACTERIAL RESISTANCE TO REACTIVE NITROGEN/OXYGEN
    Carl Nathan; Fiscal Year: 2003
    ....
  10. ROLE OF NO SYNTHASE-2 IN MURINE ALZHEIMER'S DISEASE
    Carl Nathan; Fiscal Year: 2004
    ..abstract_text> ..
  11. TARGETING DEFENSES OF MYCOBACTERIUM TUBERCULOSIS
    Carl Nathan; Fiscal Year: 2004
    ..abstract_text> ..
  12. RAP1A AND RAP1B IN THE DIAGNOSIS AND TMT - ORAL CANCER
    NISHA D SILVA; Fiscal Year: 2004
    ..The third segment involves the design of a protocol to investigate the use of rap1A in gene therapy to treat residual epithelial dysplasia or squamous cell carcinoma lesions. ..
  13. Inverted two photon laser scanning microscope for host defense
    Michael Dustin; Fiscal Year: 2008
    ..The impact on public health will be to develop better strategies to fight infections and reduce the incidence of pathogen triggered autoimmunity. [unreadable] [unreadable] [unreadable]..
  14. INTEGRATION OF STRESS AND MITOGEN SIGNALING
    Jonathan Cooper; Fiscal Year: 2001
    ..4) To map the interactions between ERK and Msk using approaches such at the two-hybrid system. 5) To clone Mapkip108 using conventional techniques. ..
  15. Chemokine Receptor Chimeras by Synthetic Gene Library
    Michael Dustin; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  16. POSTRECEPTOR DYSREGULATION IN DEPRESSION
    Yogesh Dwivedi; Fiscal Year: 2004
    ..abstract_text> ..
  17. Role of the JIP-1-p190RhoGEF Complex In Neuron Function
    WILLIAM ARTHUR; Fiscal Year: 2004
    ..Furthermore, the importance of the JIP-l-p190RhoGEF association in brain development and neuronal migration will be investigated by disrupting this complex in mutant mice . ..
  18. Rap 1-Mediated Protein Transport in Oral Cancer
    NISHA D SILVA; Fiscal Year: 2006
    ..The significance of this research is that it explores an important and novel mechanism for nucleocytoplasmic transport of pro-proliferative proteins in oral cancer, thereby identifying novel treatment targets. [unreadable] [unreadable]..
  19. Mechanochemical regulation of endothelial permeability
    Konstantin Birukov; Fiscal Year: 2007
    ....