guanine nucleotide exchange factors

Summary

Summary: Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.

Top Publications

  1. ncbi GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors
    Kent L Rossman
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Rev Mol Cell Biol 6:167-80. 2005
  2. pmc ARF family G proteins and their regulators: roles in membrane transport, development and disease
    Julie G Donaldson
    Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 12:362-75. 2011
  3. pmc The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins
    Christophe Guilluy
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Cell Biol 13:722-7. 2011
  4. doi Epac: defining a new mechanism for cAMP action
    Martijn Gloerich
    Department of Physiological Chemistry, University Medical Center, Utrecht, The Netherlands
    Annu Rev Pharmacol Toxicol 50:355-75. 2010
  5. ncbi The guanine nucleotide-binding switch in three dimensions
    I R Vetter
    , 44227 Dortmund, Germany
    Science 294:1299-304. 2001
  6. ncbi Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
    J de Rooij
    Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University, The Netherlands
    Nature 396:474-7. 1998
  7. ncbi Guanine nucleotide exchange factors for Rho GTPases: turning on the switch
    Anja Schmidt
    MRC Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, UK
    Genes Dev 16:1587-609. 2002
  8. pmc Combined immunodeficiency associated with DOCK8 mutations
    Qian Zhang
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    N Engl J Med 361:2046-55. 2009
  9. ncbi A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes
    Hiroki Nagai
    Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
    Science 295:679-82. 2002
  10. ncbi Analysis of activated GAPs and GEFs in cell lysates
    Rafael Garcia-Mata
    Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA
    Methods Enzymol 406:425-37. 2006

Detail Information

Publications419 found, 100 shown here

  1. ncbi GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors
    Kent L Rossman
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Rev Mol Cell Biol 6:167-80. 2005
    ..The failure to do so can have significant consequences and is reflected in the aberrant function of Dbl-family GEFs in some human diseases...
  2. pmc ARF family G proteins and their regulators: roles in membrane transport, development and disease
    Julie G Donaldson
    Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 12:362-75. 2011
    ..Their function is under tight spatial control, which is mediated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that catalyse GTP exchange and hydrolysis, ..
  3. pmc The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins
    Christophe Guilluy
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Cell Biol 13:722-7. 2011
    ..By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force...
  4. doi Epac: defining a new mechanism for cAMP action
    Martijn Gloerich
    Department of Physiological Chemistry, University Medical Center, Utrecht, The Netherlands
    Annu Rev Pharmacol Toxicol 50:355-75. 2010
    ..Epac1 and Epac2 function as guanine nucleotide exchange factors for the small G protein Rap...
  5. ncbi The guanine nucleotide-binding switch in three dimensions
    I R Vetter
    , 44227 Dortmund, Germany
    Science 294:1299-304. 2001
    ..Here we will try to define some underlying principles...
  6. ncbi Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
    J de Rooij
    Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University, The Netherlands
    Nature 396:474-7. 1998
    ..cAMP strongly induces the GEF activity of Epac towards Rap1 both in vivo and in vitro. We conclude that Epac is a GEF for Rap1 that is regulated directly by cAMP and that Epac is a new target protein for cAMP...
  7. ncbi Guanine nucleotide exchange factors for Rho GTPases: turning on the switch
    Anja Schmidt
    MRC Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, UK
    Genes Dev 16:1587-609. 2002
  8. pmc Combined immunodeficiency associated with DOCK8 mutations
    Qian Zhang
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    N Engl J Med 361:2046-55. 2009
    ..Recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE are features of some variants of combined immunodeficiency. The genetic causes of these variants are unknown...
  9. ncbi A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes
    Hiroki Nagai
    Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
    Science 295:679-82. 2002
    ..pneumophila. Translocation of RalF protein through the phagosomal membrane is a dot/icm-dependent process. Thus, RalF is a substrate of the Dot/Icm secretion apparatus...
  10. ncbi Analysis of activated GAPs and GEFs in cell lysates
    Rafael Garcia-Mata
    Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA
    Methods Enzymol 406:425-37. 2006
    ..This assay can be used to identify GEFs, GAPs, and effectors involved in specific cellular pathways to determine their GTPase specificity and to monitor the temporal activation of GEFs and GAPs in response to upstream signals...
  11. pmc MAP1B regulates axonal development by modulating Rho-GTPase Rac1 activity
    Carolina Montenegro-Venegas
    Department of Biology, Universidad de Chile, Santiago, Chile
    Mol Biol Cell 21:3518-28. 2010
    ..Taken together, these observations define a new and crucial function of MAP1B that we show to be required for efficient cross-talk between microtubules and the actin cytoskeleton during neuronal polarization...
  12. pmc DENN domain proteins: regulators of Rab GTPases
    Andrea L Marat
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    J Biol Chem 286:13791-800. 2011
    ..of the Rab family of small GTPases and that DENN domains function enzymatically as Rab-specific guanine nucleotide exchange factors. Thus, DENN domain proteins appear to be generalized regulators of Rab function...
  13. ncbi Epac proteins: multi-purpose cAMP targets
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Trends Biochem Sci 31:680-6. 2006
    ..In most of these processes, cAMP signaling through protein kinase A (PKA) is also involved, stressing the interconnectivity between Epac- and PKA-mediated signaling...
  14. ncbi GEFs and GAPs: critical elements in the control of small G proteins
    Johannes L Bos
    Department of Physiological Chemistry and Centre of Biomedical Genetics, UMC Utrecht Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Cell 129:865-77. 2007
    b>Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) regulate the activity of small guanine nucleotide-binding (G) proteins to control cellular functions...
  15. pmc Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene
    Manfred Kayser
    Department of Forensic Molecular Biology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
    Am J Hum Genet 82:411-23. 2008
    ..Testing markers in the HERC2-OCA2 region may be useful in forensic applications to predict eye color phenotypes of unknown persons of European genetic origin...
  16. pmc Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1
    Akiko Hayashi-Takagi
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nat Neurosci 13:327-32. 2010
    ..Furthermore, the concept of a signalosome involving disease-associated factors, such as DISC1 and glutamate, may well contribute to the multifactorial and polygenetic characteristics of schizophrenia...
  17. doi Retrograde BMP signaling controls synaptic growth at the NMJ by regulating trio expression in motor neurons
    Robin W Ball
    Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
    Neuron 66:536-49. 2010
    ..Based on our findings, we propose a model in which a retrograde BMP signal from the muscle modulates GTPase activity through transcriptional regulation of Rac GEF trio, thereby regulating the homeostasis of synaptic growth at the NMJ...
  18. doi RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity
    Stefan Schoebel
    Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, NRW, Germany
    Mol Cell 36:1060-72. 2009
    ..Thus, apparent GDI displacement by DrrA is linked directly to nucleotide exchange, suggesting a basic model for GDI displacement and specificity of Rab localization that does not require discrete GDI displacement activity...
  19. pmc Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors
    Shin ichiro Yoshimura
    Cancer Research Centre and 2 Institute of Integrative Biology, University of Liverpool, Liverpool L3 9TA, England, UK
    J Cell Biol 191:367-81. 2010
    ..DENND1C, DENND3, DENND5A/5B, MTMR5/13, and MADD activate Rab13, Rab12, Rab39, Rab28, and Rab27A/27B, respectively. Together, these findings provide a basis for future studies on Rab regulation and function...
  20. pmc RabGEFs are a major determinant for specific Rab membrane targeting
    Julia Blümer
    Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany
    J Cell Biol 200:287-300. 2013
    ..Therefore, RabGEFs are major determinants for specific Rab membrane targeting...
  21. pmc A variant in MCF2L is associated with osteoarthritis
    Aaron G Day-Williams
    Wellcome Trust Sanger Institute, Hinxton, UK
    Am J Hum Genet 89:446-50. 2011
    ..MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients...
  22. pmc The Sec7 Arf-GEF is recruited to the trans-Golgi network by positive feedback
    Brian C Richardson
    Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14850, USA
    Dev Cell 22:799-810. 2012
    ..Our results lead us to propose a model in which Arf-GEF recruitment is linked to Golgi maturation via Arf1 activation...
  23. pmc Noncanonical Notch function in motor axon guidance is mediated by Rac GTPase and the GEF1 domain of Trio
    Jeong K Song
    Axon Guidance and Neural Connectivity Unit, Basic Neuroscience Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    Dev Dyn 240:324-32. 2011
    ..We infer, therefore, that Rac is a key component of Abl signaling in Drosophila motor axons, and specifically that it is the crucial Rho GTPase in "noncanonical" Notch/Abl signaling...
  24. ncbi A bifunctional bacterial protein links GDI displacement to Rab1 activation
    Matthias P Machner
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA
    Science 318:974-7. 2007
    ..Thus, GDF and GEF activity can be promoted by a single protein, and GDF activity can coordinate Rab1 recruitment from the GDI-bound pool...
  25. pmc Coatomer-dependent protein delivery to lipid droplets
    Krishnakant G Soni
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Sci 122:1834-41. 2009
    ..Here we demonstrate that ATGL and ADRP, but not TIP47, are delivered to LDs by a pathway mediated by the COPI and COPII coatomer proteins and their corresponding regulators...
  26. ncbi A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function
    H Horiuchi
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1149-59. 1997
    ..This demonstrates that a soluble exchange factor coupled to a Rab effector translocates from cytosol to the membrane, where the complex stabilizes the GTPase in the active state...
  27. pmc A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color
    Richard A Sturm
    Institute for Molecular Bioscience, University of Queensland, Brisbane QLD 4072, Australia
    Am J Hum Genet 82:424-31. 2008
    ....
  28. ncbi Proteins regulating Ras and its relatives
    M S Boguski
    National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, Maryland 20894
    Nature 366:643-54. 1993
    ..Many of these proteins are much larger and more complex than their targets, containing multiple domains capable of interacting with an intricate network of cellular enzymes and structures...
  29. ncbi RasGRP is essential for mouse thymocyte differentiation and TCR signaling
    N A Dower
    Department of Pediatrics, University of Alberta, Edmonton Alberta, Canada, T6G 2H7
    Nat Immunol 1:317-21. 2000
    ..In Ras signaling and proliferation assays, mutant thymocytes showed a complete lack of response to DAG analogs or T cell receptor (TCR) stimulation by antibodies. Thus, TCR and DAG are linked through RasGRP to Ras signaling...
  30. ncbi The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation
    K Barrett
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown 02129, USA
    Cell 91:905-15. 1997
    ..Together, these results establish a Rho-mediated signaling pathway that is essential for the major morphogenetic events in Drosophila gastrulation...
  31. ncbi Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1
    F R Bischoff
    Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Nature 354:80-2. 1991
    ..Here we show that RCC1 specifically catalyses the exchange of guanine nucleotides on the Ran protein but not on the protein c-Ha-ras p21 (p21ras)...
  32. ncbi Par-3 controls tight junction assembly through the Rac exchange factor Tiam1
    Xinyu Chen
    Center for Cell Signaling, Department of Microbiology, HSC, University of Virginia, Charlottesville, Virginia 22908, USA
    Nat Cell Biol 7:262-9. 2005
    ..These results define a critical function for Par-3 in tight junction assembly, and reveal a novel mechanism through which Par-3 engages in the spatial regulation of Rac activity and establishment of epithelial polarity...
  33. ncbi The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor
    Takahiro Murata
    Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
    Nat Cell Biol 8:971-7. 2006
    ....
  34. pmc RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity
    W T Arthur
    Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Biol Cell 12:2711-20. 2001
    ..Taken together, these data demonstrate that integrin-triggered RhoA inhibition by p190RhoGAP enhances spreading and migration by regulating cell protrusion and polarity...
  35. pmc A positive feedback loop stabilizes the guanine-nucleotide exchange factor Cdc24 at sites of polarization
    Anne Christine Butty
    Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, CH 1066 Epalinges VD, Switzerland
    EMBO J 21:1565-76. 2002
    ..Thus, our results suggest that Bem1 functions in a positive feedback loop: local activation of Cdc24 produces Cdc42-GTP, which recruits Bem1. In turn, Bem1 stabilizes Cdc24 at the site of polarization, leading to apical growth...
  36. 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...
  37. pmc Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells
    Tetsuhisa Otani
    Graduate School of Biostudies, Kyoto University, Yoshida Honmachi, Kyoto 606 8501, Japan
    J Cell Biol 175:135-46. 2006
    ..These results suggest that Tuba controls the shaping of cell junctions through the local activation of Cdc42 and its effectors...
  38. pmc Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate
    Xudong Wu
    Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 108:18672-7. 2011
    ..They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form...
  39. pmc Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer
    Maria Soledad Sosa
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 40:877-92. 2010
    ..In addition to the prognostic and therapeutic implications, our findings reveal an ErbB effector pathway that is crucial for breast cancer progression...
  40. pmc Ric-8A and Gi alpha recruit LGN, NuMA, and dynein to the cell cortex to help orient the mitotic spindle
    Geoffrey E Woodard
    B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, 10 Center Drive, MSC 1888, Bethesda, MD 20892 1752, USA
    Mol Cell Biol 30:3519-30. 2010
    ..These data indicate that Ric-8A signaling leads to assembly of a cortical signaling complex that functions to orient the mitotic spindle...
  41. pmc Control of synapse development and plasticity by Rho GTPase regulatory proteins
    Kimberley F Tolias
    Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
    Prog Neurobiol 94:133-48. 2011
    ..Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and inhibited by GTPase-activating proteins (GAPs)...
  42. ncbi A family of cAMP-binding proteins that directly activate Rap1
    H Kawasaki
    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology MIT, Cambridge, MA, 02139, USA
    Science 282:2275-9. 1998
    ..Our findings suggest the need to reformulate concepts of cAMP-mediated signaling to include direct coupling to Ras superfamily signaling...
  43. 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...
  44. ncbi cAMP acts on exchange protein activated by cAMP/cAMP-regulated guanine nucleotide exchange protein to regulate transmitter release at the crayfish neuromuscular junction
    Ning Zhong
    Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California 9472, USA
    J Neurosci 25:208-14. 2005
    ..Epac also mediates the enhancement of tagged synapses. Thus, the cAMP-dependent enhancement of transmission is mediated by two separate pathways, neither of which involves protein kinase A...
  45. ncbi cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically to promote PC-12 cell neurite extension
    Anne E Christensen
    Department of Anatomy and Cell Biology, University of Bergen, 5009 Bergen, Norway
    J Biol Chem 278:35394-402. 2003
    ..We therefore conclude that cAMP-induced neurite outgrowth is mediated by both Epac and cAPK...
  46. 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...
  47. pmc A Rab GAP cascade defines the boundary between two Rab GTPases on the secretory pathway
    Félix E Rivera-Molina
    Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 106:14408-13. 2009
    ..Rabs are activated by specific guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs)...
  48. 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
    ..Our data provide genetic evidence that the CD4(+) and CD4(-) iNKT cells are distinct sublineages with differential signaling requirements for their development...
  49. pmc DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses
    Yosuke Harada
    Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    Blood 119:4451-61. 2012
    ..Therefore, DOCK8 regulates interstitial DC migration by controlling Cdc42 activity spatially...
  50. pmc ARF1 and GBF1 generate a PI4P-enriched environment supportive of hepatitis C virus replication
    Leiliang Zhang
    Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    PLoS ONE 7:e32135. 2012
    ..Moreover, the vesicular transport proteins ARF1 and GBF1 colocalized with PI4KIIIβ and were both required for HCV replication. During authentic HCV infection, PI4P plays an integral role in virus replication...
  51. ncbi PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1
    Takashi Nishimura
    Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi 466 8550, Japan
    Nat Cell Biol 7:270-7. 2005
    ..We propose that the PAR-6-PAR-3 complex mediates Cdc42-induced Rac activation by means of STEF/Tiam1, and that this process seems to be required for the establishment of neuronal polarity...
  52. pmc Rab1b interacts with GBF1 and modulates both ARF1 dynamics and COPI association
    Pablo Monetta
    Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Departamento Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba 5000, Argentina
    Mol Biol Cell 18:2400-10. 2007
    ..Our data support a model where Rab1b-GTP induces GBF1 recruitment at the ERES interface and at the Golgi complex where it is required for COPII/COPI exchange or COPI vesicle formation, respectively...
  53. ncbi Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2
    H Bea Kuiperij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
    Biochim Biophys Acta 1593:141-9. 2003
    ..We conclude that both PDZ-GEF1 and 2 are specific for Rap1 and Rap2 and unresponsive to cAMP and various other nucleotides...
  54. pmc Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis
    Stephen J Terry
    Department of Cell Biology, UCL Institute of Ophthalmology, University College London, Bath Street, London, UK
    Nat Cell Biol 13:159-66. 2011
    ....
  55. pmc Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP
    Tadao Shibasaki
    Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe, Hyogo 650 0017, Japan
    Proc Natl Acad Sci U S A 104:19333-8. 2007
    ..Taken together, these data indicate that Epac2/Rap1 signaling is essential in regulation of insulin granule dynamics by cAMP, most likely by controlling granule density near the plasma membrane...
  56. ncbi P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac
    Heidi C E Welch
    Inositide Laboratory, Cambridge CB2 4AT, United Kingdom
    Cell 108:809-21. 2002
    ..P-Rex1 appears to be a coincidence detector in PtdIns(3,4,5)P3 and Gbetagamma signaling pathways that is particularly adapted to function downstream of heterotrimeric G proteins in neutrophils...
  57. pmc Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome
    Karin R Engelhardt
    Department of Immunology and Molecular Pathology, Royal Free Hospital and University College London, London, UK
    J Allergy Clin Immunol 124:1289-302.e4. 2009
    ..In the remaining patients with hyper-IgE syndrome, the genetic etiology has not yet been identified...
  58. pmc Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines
    Zhong Xie
    Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Neuron 56:640-56. 2007
    ....
  59. ncbi Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin
    Peter Penzes
    Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Neuron 37:263-74. 2003
    ..This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity...
  60. pmc Trio is a key guanine nucleotide exchange factor coordinating regulation of the migration and morphogenesis of granule cells in the developing cerebellum
    Ya Jing Peng
    Model Animal Research Center and MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing 210061, China
    J Biol Chem 285:24834-44. 2010
    ..Trio may serve as a signal integrator decoding extrinsic signals to Rho GTPases for cytoskeleton organization...
  61. pmc Symmetry-breaking polarization driven by a Cdc42p GEF-PAK complex
    Lukasz Kozubowski
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Curr Biol 18:1719-26. 2008
    ..Cdc42p concentrates at a random cortical site during symmetry breaking in a manner that requires the scaffold protein Bem1p. The mechanism whereby Bem1p promotes this polarization was unknown...
  62. pmc Targeting and activation of Rac1 are mediated by the exchange factor beta-Pix
    Jean Paul ten Klooster
    Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, Netherlands
    J Cell Biol 172:759-69. 2006
    ..These data provide a model for the intracellular targeting and localized activation of Rac1 through its exchange factor beta-Pix...
  63. pmc The Connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit from early endosomes
    Patrick D Allaire
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    Mol Cell 37:370-82. 2010
    ..Our data reveal an enzymatic activity for a DENN domain and demonstrate that distinct Rab GTPases can recruit a common protein machinery to various sites within the endosomal network to establish cargo-selective recycling pathways...
  64. pmc Dendritic spine dynamics--a key role for kalirin-7
    Peter Penzes
    Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Trends Neurosci 31:419-27. 2008
    ....
  65. pmc The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma
    Bodour Salhia
    Arthur and Sonia Labatt Brain Tumor Research Centre, Cancer and Cell Biology Division, The Hospital for Sick Children, The University of Toronto, Toronto, Canada
    Am J Pathol 173:1828-38. 2008
    ..Here, we aim to identify Rac-activating guanine nucleotide exchange factors (GEFs) that mediate glioblastoma invasiveness...
  66. ncbi Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell
    S Stender
    Max von Pettenkofer Institut, Munich, Germany
    Mol Microbiol 36:1206-21. 2000
    ..In conclusion, as a result of SopE2 all S. typhimurium strains tested have the capacity to activate Cdc42 signalling inside host cells which is important to ensure efficient entry...
  67. pmc Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphate-binding effector protein of Legionella pneumophila
    Eva Brombacher
    Institute of Microbiology, ETH Zurich, Wolfgang Pauli Strasse 10, 8093 Zurich, Switzerland
    J Biol Chem 284:4846-56. 2009
    ..Thus, L. pneumophila exploits PtdIns(4)P produced by PtdIns 4-kinase IIIbeta to anchor the effectors SidC and SidM to LCVs...
  68. pmc Conserved functions of membrane active GTPases in coated vesicle formation
    Thomas J Pucadyil
    Department of Cell Biology, The Scripps Research Institute TSRI, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 325:1217-20. 2009
    ....
  69. ncbi Rho and Rac take center stage
    Keith Burridge
    Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Cell 116:167-79. 2004
    ..of Rho proteins is regulated downstream from growth factor receptors and cell adhesion molecules by guanine nucleotide exchange factors and GTPase activating proteins...
  70. doi Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression
    Hans Eiberg
    Department of Cellular and Molecular Medicine, Section IV Build 24 4, Panum Institute, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen, Denmark
    Hum Genet 123:177-87. 2008
    ..In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color...
  71. pmc High-affinity binding of phosphatidylinositol 4-phosphate by Legionella pneumophila DrrA
    Stefan Schoebel
    Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, North Rhine Westphalia, Germany
    EMBO Rep 11:598-604. 2010
    ..A detailed kinetic investigation of its interaction with PtdIns(4)P reveals that DrrA binds to this phospholipid with, as yet unprecedented, high affinity, suggesting that DrrA can sense a very low abundance of the lipid...
  72. ncbi A role for Rac in Tiam1-induced membrane ruffling and invasion
    F Michiels
    The Netherlands Cancer Institute, Division of Cell Biology, Amsterdam
    Nature 375:338-40. 1995
    ..Moreover, T-lymphoma cells expressing V12Rac1 become invasive, indicating that the Tiam1-Rac signalling pathway could be operating in the invasion and metastasis of tumour cells...
  73. pmc De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila
    M Ramona Neunuebel
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Science 333:453-6. 2011
    ..L. pneumophila mutants lacking SidD were defective for Rab1 removal from LCVs, identifying SidD as the missing link connecting the processes of early Rab1 accumulation and subsequent Rab1 removal during infection...
  74. 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
    ..RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation...
  75. pmc DRhoGEF2 encodes a member of the Dbl family of oncogenes and controls cell shape changes during gastrulation in Drosophila
    U Hacker
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115 USA
    Genes Dev 12:274-84. 1998
    ....
  76. pmc Phylogenetic analysis of Sec7-domain-containing Arf nucleotide exchangers
    Randal Cox
    Department of Biochemistry, Laboratory for Molecular Biology, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Mol Biol Cell 15:1487-505. 2004
    ..Determination of the importance of these conserved elements in Arf exchange activity and other cellular functions is now possible...
  77. ncbi GEP100 links epidermal growth factor receptor signalling to Arf6 activation to induce breast cancer invasion
    Masaki Morishige
    Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565 0874, Japan
    Nat Cell Biol 10:85-92. 2008
    ..Our results indicate that GEP100 links EGFR signalling to Arf6 activation to induce invasive activities of some breast cancer cells, and hence may contribute to their metastasis and malignancy...
  78. ncbi The Human Rho-GEF trio and its target GTPase RhoG are involved in the NGF pathway, leading to neurite outgrowth
    Soline Estrach
    CRBM CNRS, UPR 1086 CNRS, 1919 Route de Mende, 34293 5, Montpellier Cedex, France
    Curr Biol 12:307-12. 2002
    ..b>Guanine nucleotide exchange factors (GEFs) activate Rho-GTPases by accelerating GDP/GTP exchange...
  79. pmc Structure-function analysis of VPS9-ankyrin-repeat protein (Varp) in the trafficking of tyrosinase-related protein 1 in melanocytes
    Kanako Tamura
    Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba ku, Sendai, Miyagi 980 8578, Japan
    J Biol Chem 286:7507-21. 2011
    ....
  80. 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...
  81. pmc Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy
    Molly A Lynch-Day
    Departments of Molecular, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 2216, USA
    Proc Natl Acad Sci U S A 107:7811-6. 2010
    ..The TRAPP complexes are multimeric guanine nucleotide exchange factors (GEFs) that activate the Rab GTPase Ypt1, which is required for secretion...
  82. pmc Fission yeast Nod1 is a component of cortical nodes involved in cell size control and division site placement
    Isabelle Jourdain
    Cell Regulation Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom
    PLoS ONE 8:e54142. 2013
    ..At later stages of cytokinesis, these various rings appeared inter-fitted rather than merged. This study brings a new slant to the understanding of CAR assembly and function...
  83. pmc Rab GEFs and GAPs
    Francis Barr
    University of Liverpool, Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK
    Curr Opin Cell Biol 22:461-70. 2010
    ..Recent structural and cell biological studies shed new light on the mechanisms of Rab GEF and GAP action, and the cellular trafficking pathways they act in...
  84. pmc Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation
    L Zeng
    Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Mol Cell Biol 20:9212-24. 2000
    ..We conclude that Vav3 mediates RPTK signaling and regulates GTPase activity, its native and mutant forms are able to modulate cell morphology, and it has the potential to induce cell transformation...
  85. doi AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression
    Ralf Scholz
    Center for Molecular Neurobiology ZMNH, University of Hamburg, Hamburg, Germany
    Neuron 66:768-80. 2010
    ..We conclude that BRAG2-mediated Arf6 activation triggered by AMPA receptors is the convergent step of different forms of LTD, thus providing an essential mechanism for the control of vesicle formation by endocytic cargo...
  86. pmc Kinetic studies of the Arf activator Arno on model membranes in the presence of Arf effectors suggest control by a positive feedback loop
    Danièle Stalder
    Institut de Pharmacologie Moleculaire et Cellulaire, Université de Nice Sophia Antipolis et CNRS, 06560 Valbonne, France
    J Biol Chem 286:3873-83. 2011
    ..This property of Arno might provide an explanation for its function in signaling pathways that, once triggered, must move forward decisively...
  87. doi Guanine nucleotide exchange factors for RhoGTPases: good therapeutic targets for cancer therapy?
    Galit Lazer
    Developmental Biology and Cancer Research, IMRIC, Hebrew University Hadassah Medical School, Jerusalem, Israel
    Cell Signal 23:969-79. 2011
    ..RhoGTPase activity is regulated by a number of protein families: guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and guanine nucleotide-dissociation inhibitors (GDIs)...
  88. ncbi Kalirin, a cytosolic protein with spectrin-like and GDP/GTP exchange factor-like domains that interacts with peptidylglycine alpha-amidating monooxygenase, an integral membrane peptide-processing enzyme
    M R Alam
    Departments of Neuroscience and Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Biol Chem 272:12667-75. 1997
    ....
  89. pmc Specific functions of BIG1 and BIG2 in endomembrane organization
    Frédéric Boal
    Department of Biochemistry, Cell Biology Laboratories, University of Bristol School of Medical Sciences, Bristol, United Kingdom
    PLoS ONE 5:e9898. 2010
    ..Arfs are activated by guanine nucleotide exchange factors (GEFs) which results in their recruitment to membranes and subsequent engagement with Arf-effectors,..
  90. ncbi Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains
    J K Klarlund
    Program in Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, 373 Plantation Street, Worcester, MA 01605, USA
    Science 275:1927-30. 1997
    ..GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking...
  91. ncbi Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases
    Adam Shutes
    Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 282:35666-78. 2007
    ..Taken together, our results suggest that EHT 1864 selectively inhibits Rac downstream signaling and transformation by a novel mechanism involving guanine nucleotide displacement...
  92. pmc Behavioral and morphological responses to cocaine require kalirin7
    Drew D Kiraly
    Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, USA
    Biol Psychiatry 68:249-55. 2010
    ..Despite numerous reports of these findings, the molecular mechanisms leading to these morphological, biochemical, and behavioral changes remain unclear...
  93. pmc Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5
    Sangho Lee
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health NIH, Bethesda, Maryland 20892, USA
    Nat Struct Mol Biol 13:264-71. 2006
    ..The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme...
  94. ncbi Ras-activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1
    G G Tall
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Dev Cell 1:73-82. 2001
    ..RIN1 also contains a region homologous to the catalytic domain of Vps9p-like Rab guanine nucleotide exchange factors (GEFs)...
  95. pmc Cell physiology of cAMP sensor Epac
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Physiol 577:5-15. 2006
    ..an acronym for the exchange proteins activated directly by cyclic AMP, a family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs) that mediate protein kinase A (PKA)-independent signal transduction properties of the ..
  96. pmc GEP100-Arf6-AMAP1-cortactin pathway frequently used in cancer invasion is activated by VEGFR2 to promote angiogenesis
    Ari Hashimoto
    Department of Molecular Biology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    PLoS ONE 6:e23359. 2011
    ..The GEP100-Arf6-AMAP1-cortactin pathway, activated by receptor tyrosine kinases, appears to be common in angiogenesis and cancer invasion and metastasis, and provides their new therapeutic targets...
  97. doi Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis
    Kuan Chung Su
    Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK
    Dev Cell 21:1104-15. 2011
    ..We propose that targeting of Ect2 to the equatorial membrane represents a key step in the delivery of the cytokinetic signal to the cortex...
  98. pmc Muscle giants: molecular scaffolds in sarcomerogenesis
    Aikaterini Kontrogianni-Konstantopoulos
    Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Physiol Rev 89:1217-67. 2009
    ....
  99. pmc Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry (DXMS)
    Sheng Li
    Department of Medicine and Biomedical Sciences Graduate program, University of California, San Diego, La Jolla, California 92093 0656, USA
    J Biol Chem 286:17889-97. 2011
    ....
  100. pmc Control of cell adhesion dynamics by Rap1 signaling
    Benjamin Boettner
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Curr Opin Cell Biol 21:684-93. 2009
    ..Furthermore, we will describe novel findings on the Rap activator PDZ-GEF in the regulation of cell-cell adhesion between epithelial cells and within a stem cell niche...
  101. pmc The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits
    David P Siderovski
    Department of Pharmacology, UNC Lineberger Comprehensive Cancer Center, and UNC Neuroscience Center, The University of North Carolina at Chapel Hill, CB 7365, 1106 M E Jones Building, Chapel Hill, NC 27599 7365 USA
    Int J Biol Sci 1:51-66. 2005
    ..These new roles include the RGS-box-containing, RhoA-specific guanine nucleotide exchange factors (RGS-RhoGEFs) that serve as Galpha effectors to couple 7TM and semaphorin receptor signaling to ..

Research Grants69

  1. Rac GTPase signaling during embryonic salivary gland branching morphogenesis
    Sharon Sequeira; Fiscal Year: 2012
    ....
  2. Diverse Roles for RIC8 During G Protein Signaling in Fungi
    Katherine A Borkovich; Fiscal Year: 2012
    ..G protein coupled receptors (GPCRs) have been characterized as guanine nucleotide exchange factors (GEFs) for Ga subunits...
  3. Dissecting the role of one neuronal RhoGEF amongst many: the Kalirin-7 null mouse
    Richard E Mains; Fiscal Year: 2012
    ..Mental retardation is associated with deficits in individual Rho proteins, in the guanine nucleotide exchange factors (GEFs) that activate Rho proteins and in downstream targets of activated Rho proteins...
  4. SIGNALING THROUGH RHO GTP/GDP EXCHANGE FACTORS
    Philip B Wedegaertner; Fiscal Year: 2013
    ..The research in this application will provide new knowledge about the functions of RhoGEFs and thus better define how the RhoGEFs can be therapeutically inhibited in disease without affecting their critical normal functions. ..
  5. STRUCTURE AND FUNCTION OF PAXILLIN
    Christopher E Turner; Fiscal Year: 2012
    ..role in this regulation but the mechanisms controlling the activity of their key regulators, the guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) remain poorly understood...
  6. FUNCTION OF THE RAS RELATED RAL PROTEINS
    LARRY FEIG; Fiscal Year: 2009
    ..RalA and RalB are members of the Ras superfamily that become activated by a distinct set of guanine nucleotide exchange factors (Ral-GEFs), like RalGDS, in response to a variety of extracellular signals...
  7. MOLECULAR MODELS OF IMMUNE-MEDIATED VASCULAR INJURY
    Jeffrey R Bender; Fiscal Year: 2012
    ....
  8. Pososome Regulated Monocyte/Macrophage Tissue Infiltration
    Dianne Cox; Fiscal Year: 2013
    ....
  9. Function of the Ras Related Ral Protein
    LARRY FEIG; Fiscal Year: 2013
    ..RalA and RalB are members of the Ras superfamily that become activated by a distinct set of guanine nucleotide exchange factors, like RalGDS, in response to a variety of extracellular signals...
  10. Hepatocyte Nitric Oxide Synthase Regulation by Glucagon and Insulin
    Brian G Harbrecht; Fiscal Year: 2012
    ..By defining these mechanisms, we will provide a framework for understanding the basic cellular events in shock and sepsis, which may lead to novel cellular-based therapies for critically ill patients. ..
  11. Calcium-sensing Receptor and Keratinocyte Differentiation
    Chia Ling Tu; Fiscal Year: 2013
    ..Successful completion of this project will greatly advance our knowledge of skin cell differentiation and help understanding the pathogenesis of various skin disorders manifesting abnormal differentiation. ..
  12. Signaling Connections Controlling Cell Motility and Invasion
    David D Schlaepfer; Fiscal Year: 2013
    ..This multi-faceted approach will yield a comprehensive understanding of Rgnef-FAK signaling axis within fibroblasts and ovarian cancer cells and provide new insights into pathways driving disease progression. ..
  13. Protein Kinase C Signaling Mechanisms in Cancer
    Alan P Fields; Fiscal Year: 2013
    ....
  14. Rho- and GPCR-mediated signaling through novel cellular effectors
    Joan Heller Brown; Fiscal Year: 2012
    ....
  15. Elucidating the role of the eIF2alpha kinase PERK in synaptic plasticity and memo
    MY AI TRINH; Fiscal Year: 2010
    ....
  16. Novel Molecules in Calcium Signaling in Platelets
    Wolfgang Bergmeier; Fiscal Year: 2013
    ..CD-GEF proteins are guanine nucleotide exchange factors for Ras family small GTPases. They are regulated by both by Ca2+ and/or diacylglycerol (DAG)...
  17. Very Late Antigen Integrin Activity on T Cells
    Yoji Shimizu; Fiscal Year: 2010
    ....
  18. Microtubule-associated Rac
    Anna Birukova; Fiscal Year: 2013
    ..These studies will characterize novel barrier protective mechanisms and identify new protein targets for future therapies aimed at prevention of the pulmonary vascular barrier dysfunction associated with acute lung injury. ..
  19. Role of p190RhoGEF (Rgnef) in cell motility and tumor progression
    Nichol L G Miller; Fiscal Year: 2013
    ..The results will enhance our current understanding of intracellular signaling pathways promoting ovarian carcinoma tumor progression. ..
  20. Multimeric Signaling Complexes in PRLr Transduction
    Charles V Clevenger; Fiscal Year: 2013
    ..Third, the in vivo biologic relevance of the Nek3/Vav2 complex will be addressed through the study of Nek3-/- mice and breast cancer cell xenografts with altered levels of Nek3 activity. ..
  21. IDENTIFICATION OF GENES ASSOCIATED WITH MYOBLAST FUSION
    Susan M Abmayr; Fiscal Year: 2012
    ..The focus of our research is to examine the mechanisms and essential genes through which cells find each other in the embryo and initiate the process of fusion. ..
  22. Regulation of Rho family GTPases by heterotrimeric G proteins
    BARRY S KREUTZ; Fiscal Year: 2013
    ..The results from this project will make crucial contribution to understand advancement of cancer phenotypes and form a solid basis for future anti-cancer drug development. ..
  23. The RAN GTPase
    Ian G Macara; Fiscal Year: 2013
    ..Finally, we discovered that in HeLa cells, which express the E7 oncoprotein, RB is not detectably methylated. We will address the underlying mechanism that blocks RB methylation in these cells. ..
  24. Mechanistic Studies of Ras-MAPK Signals: Specialzed Cues for the T cell Lineage?
    Jeroen Roose; Fiscal Year: 2011
    Thymocytes and peripheral T cells express two types of Ras Guanine nucleotide Exchange Factors (RasGEFs), SOS and RasGRP, which can activate Ras and Ras[unreadable] downstream MAP kinase (MAPK) pathways in response to T cell receptor (..
  25. Lipid Signaling in Chemotaxis
    Miho Iijima; Fiscal Year: 2013
    ..The long-term goal of our study is to understand how chemotaxis works and how defects in chemotaxis cause human diseases using a variety of approaches including genetics, biochemistry, cell biology and proteomics. ..
  26. MOLECULAR BASIS OF ANTIDIABETOGENIC HORMONE ACTION
    George G Holz; Fiscal Year: 2010
    ..signaling mechanism that uses the second messenger cAMP to activate cAMP- regulated guanine nucleotide exchange factors designated as Epad and Epac2 (the Exchange Proteins directly Activated by Cyclic AMP)...
  27. Rho-mediated Signaling in Lung Endothelial Cells Induced by Neutrophil Adhesion
    KLAUS MICHAEL HAHN; Fiscal Year: 2013
    ..Aim 2 will identify and manipulate guanine nucleotide exchange factors (GEFs) that are downstream of E-selectin and ICAM-1 and that regulate Rho protein activity...
  28. Protective role of ANP in the models of acute lung injury
    Anna Birukova; Fiscal Year: 2013
    ..We believe that these studies may identify novel protein targets and propose new therapies for prevention of pulmonary vascular barrier dysfunction associated with acute lung inflammation and injury. ..
  29. Cell Adhesion and the Regulation of Rho GTPases
    Keith Burridge; Fiscal Year: 2013
    ..Having recently identified guanine nucleotide exchange factors, such as Lsc, that are involved in this process, we aim to determine the signaling pathways that ..
  30. Epigenetic Consequences of Prenatal Alcohol Exposure
    Eva E Redei; Fiscal Year: 2013
    ..Identifying the mechanisms and potential reversibility of transgenerational effects and devising novel interventions in the animal model of FAE is a major goal that could potentially be beneficial for human FAE. ..
  31. Role of Ypt/Rab GTPases in intra-cellular Trafficking
    Nava Segev; Fiscal Year: 2013
    ....
  32. Regulation of androgen receptor activity in prostate cancer cells in an aged mous
    STEPHANIE OLGA PEACOCK; Fiscal Year: 2013
    ..abstract_text> ..
  33. ErbB receptor signaling via small G-proteins in breast cancer
    MARCELO GABRIEL KAZANIETZ; Fiscal Year: 2013
    ..Studies will be pursued in cellular and animal models to elucidate its relevance in the etiology of breast cancer and in the context of ErbB receptors. ..
  34. Neurotrophic Factor Regulation of Gene Expression
    Michael E Greenberg; Fiscal Year: 2012
    ....
  35. Regulation of Synaptic Transmission by Gq
    Michael Ailion; Fiscal Year: 2009
    ..This proposal aims to understand how such chemicals affect communication between cells in the nervous system so that better drugs can be designed to treat these disorders. ..
  36. Rac GTPase-Specific Small Molecular Inhibitors
    Yi Zheng; Fiscal Year: 2013
    ..the interaction between Rac GTPase of the Rho family and their regulatory proteins, the Dbl family guanine nucleotide exchange factors (GEFs) in particular, to the design of novel approaches to target deregulated Rac activities in ..
  37. Differential regulation of Ras nucleotide exchange factors
    JEFFREY SCOTT IWIG; Fiscal Year: 2012
    ..Ras cycles between active GTP-bound and inactive GDP-bound states, which is controlled by Ras guanine nucleotide exchange factors (GEFs) and guanine nucleotide activating proteins (GAPs) and insensitivity of Ras to these proteins,..
  38. Understanding the Role of Epac2 in Cognitive Function
    Ruoqi Gao; Fiscal Year: 2012
    ..Our studies will contribute to the understanding behind these processes, and perhaps allow us to begin to comprehend the pathogenesis of several neuropsychiatric diseases, such as Autism Spectrum Disorders. ..
  39. Investigation of calcium signaling in Caenorhabditis elegans
    Kenneth Norman; Fiscal Year: 2013
    ....
  40. Molecular Mechanisms of RhoA-mediated Ca2+Sensitization in Vascular Smooth Muscle
    Avril V Somlyo; Fiscal Year: 2013
    ..is well understood that RhoA, a ubiquitous molecular switch, is controlled by many different GEFs (guanine nucleotide exchange factors) and GAPs (GTPase activating proteins), which either load RhoA with GTP (GEFs) or downregulate it ..
  41. Role of DOCK8 in B Cell Function
    RAIF SALIM GEHA; Fiscal Year: 2013
    ..Since DOCK8 deficiency predisposes to autoimmunity, allergy and cancer, its study is likely to provide novel and important insights into the pathogenesis of these common conditions. ..
  42. Targeting the Fn14-Rac1 signaling pathway in invasive gliomas
    Nhan L Tran; Fiscal Year: 2012
    ..abstract_text> ..
  43. RGS proteins as novel integrators of G protein and MAPK signaling
    John R Hepler; Fiscal Year: 2013
    ..Impact: These studies will provide key insight about RGS14 as a novel regulator and integrator of neurotransmitter signaling events that modulate neuronal plasticity, learning and memory. ..
  44. BARRIER FUNCTION OF THE GI TRACT IN HEALTH AND DISEASE
    W Allan Walker; Fiscal Year: 2013
    ..abstract_text> ..
  45. Structure and function of BCAR1 and BCAR3 association in breast cancer malignancy
    Stefan J Riedl; Fiscal Year: 2013
    ..Thus, this work will ultimately provide a new basis for developing treatment options to overcome cancer drug resistance. ..
  46. Mechanism of G protein Activation by Ric-8A
    Stephen R Sprang; Fiscal Year: 2013
    ....
  47. Nuclear GTPase PIKE Regulation and Functions
    Keqiang Ye; Fiscal Year: 2013
    ..abstract_text> ..
  48. STRUCTURAL ANALYSIS OF G PROTEIN REGULATORY MECHANISMS
    STEPHEN SPRANG; Fiscal Year: 2009
    ..The structural models obtained from these results, and the functional hypotheses inferred therefrom will be tested by activity assays of structure- based site directed mutants. ..
  49. GENETIC ANALYSIS OF RAS AND G PROTEIN FUNCTION
    LARRY FEIG; Fiscal Year: 2013
    ..of this proposal is on GRF1 and GRF2, which form a family of multi-catalytic, calcium- stimulated, guanine nucleotide exchange factors that have the potential to activate both Ras and Rac GTPases...
  50. Role of kalirin signaling in synaptic plasticity
    Peter Penzes; Fiscal Year: 2013
    ..As both spine density and kalirin expression are reduced in schizophrenic patients'brains, these studies are expected to provide important insight into the mechanisms of spine pathology in mental disorders. 1 ..
  51. ELMO1, Dock180 and Glioma Invasion
    Shi Yuan Cheng; Fiscal Year: 2012
    ..The proposed work has translational significance in providing new insights into intrinsic invasiveness of glioma cells and exploring approaches that impact the response to existing glioma therapies. ..
  52. 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. ..
  53. Regulation of Arf GTPase activation at the trans-Golgi network
    J Christopher Fromme; Fiscal Year: 2013
    ..We expect that our research will lead to a clear model for how activation of Arf GTPases at the Golgi is regulated spatiotemporally. ..
  54. PTSD-like phenotype of mice lacking GIT2
    Richard T Premont; Fiscal Year: 2011
    ..Together with the alpha-PIX and beta-PIX proteins (themselves guanine nucleotide exchange factors for Rho family small GTP-binding proteins), GIT proteins form an oligomeric signaling scaffolding ..
  55. Cytoskeletal Oscillations: Mathematical Modeling Integrated with Experiments
    Kenneth A Jacobson; Fiscal Year: 2013
    ..The wave front is propagated by a positive feedback loop involving the recruitment of guanine nucleotide exchange factors (GEFs), which accelerate activation of RhoA...
  56. Elucidating a G-protein signaling pathway in E. histolytica amoebic colitis
    Dustin E Bosch; Fiscal Year: 2013
    ..The proposed training and research plans will provide the skills and knowledge base necessary for a successful career as a gastroenterologist physician-scientist. ..
  57. Regulation of Glioma Cell Migration by RasGRP3
    Chaya Brodie; Fiscal Year: 2010
    ..abstract_text> ..
  58. Characterization of GEFT AS a Novel Glioblastoma Oncogene
    MILAN GIRISH CHHEDA; Fiscal Year: 2013
    ..With the most aggressive therapy, median survival is 14.6 months. I propose to characterize a gene, GEFT, that might play a role in formation and maintenance of these tumors...
  59. Elucidating the Molecular Mechanisms of Ect2 in cytokinesis and oncogenesis
    DANIELLE RYAN COOK; Fiscal Year: 2012
    ..activity of Rho GTPase is the result of abnormalities in activating proteins called RhoGEFs (guanine nucleotide exchange factors). My studies are focused on one RhoGEF, Ect2 (Epithelial cell transforming sequence 2)...
  60. Novel therapeutic inhibition of the Rac oncogene in pancreatic cancer
    MARK A MC NIVEN; Fiscal Year: 2012
    ..The information gathered from this proposal will provide the basis of an exciting, important, and novel pre-clinical trial toward treating this lethal disease. ..
  61. Rap1 in VEGF signaling in endothelial cells
    Magdalena Chrzanowska-Wodnicka; Fiscal Year: 2013
    ..Knowledge gained through this research is expected to enable successful modulation of VEGF responses by manipulating specific Rap1 isoform activity. ..
  62. Role of TTK/Mps-1 upregulation by Ral GTPase activation in pancreatic oncogenesis
    Jeran K Stratford; Fiscal Year: 2013
    ..Taken together, these studies will require me to master an array of experimental techniques, while preparing me to do both basic and translational research. ..
  63. MOLECULAR MECHANISMS OF MAST CELL SECRETION--ROLE OF RAB
    Bridget Wilson; Fiscal Year: 1999
    ..supports to purify and characterize SH3 domain-containing proteins which may serve as adaptors, guanine nucleotide exchange factors, or both for rab3D...
  64. MOLECULAR MECHANISMS OF NUCLEAR PROTEIN IMPORT
    Mary Moore; Fiscal Year: 1999
    ..A variety of techniques will be used to address this question including immunolocalization and immunoprecipitations and the tracking of labelled import factors during import. ..
  65. METABLASTIN AND THE CONTROL OF CELL DIVISION
    ULRICH SCHUBART; Fiscal Year: 1999
    ..Mip1 is novel but may be related to the dbl proto-oncogene family of guanine nucleotide exchange factors for certain Ras-related GTP-binding proteins...
  66. MECHANISMS & REGULATION OF PROTEIN SYNTHESIS
    ALBERT WAHBA; Fiscal Year: 1992
    ..The isolated clones will be characterized by restriction mapping, nucleotide sequencing, and their derived amino acid sequence. The sequencing of the genomic clones for ..
  67. Induction of Macrophage iNOS by Salmonella
    BOBBY CHERAYIL; Fiscal Year: 2006
    ..The results of these studies will shed light on a novel function of SopE and SopE2 and will also improve understanding of the mechanisms that regulate iNOS expression. ..
  68. REGULATION OF MAST CELL DEVELOPMENT AND FUNCTION
    STEPHEN JOSEPH GALLI; Fiscal Year: 2010
    ..abstract_text> ..
  69. RHOA EFFECTOR IN HIV-1 REPLICATION AND PATHOGENESIS
    Lishan Su; Fiscal Year: 2004
    ..abstract_text> ..