ARHGEF2

Summary

Gene Symbol: ARHGEF2
Description: Rho/Rac guanine nucleotide exchange factor (GEF) 2
Alias: GEF, GEF-H1, GEFH1, LFP40, P40, Rho/Rac guanine nucleotide exchange factor 2, guanine nucleotide exchange factor H1, microtubule-regulated Rho-GEF, proliferating cell nucleolar antigen p40, rho guanine nucleotide exchange factor 2
Species: human

Top Publications

  1. pmc The epidermal growth factor receptor mediates tumor necrosis factor-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular epithelium
    Eli Kakiashvili
    Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael s Hospital, and Department of Surgery, University of Toronto, Toronto, Ontario M5B 1W8, Canada
    J Biol Chem 286:9268-79. 2011
  2. ncbi p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor
    Frank T Zenke
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 279:18392-400. 2004
  3. pmc GEF-H1 couples nocodazole-induced microtubule disassembly to cell contractility via RhoA
    Yuan Chen Chang
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Mol Biol Cell 19:2147-53. 2008
  4. pmc Guanine nucleotide exchange factor-H1 regulates cell migration via localized activation of RhoA at the leading edge
    Perihan Nalbant
    Departments of Immunology and Microbial Science, and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Mol Biol Cell 20:4070-82. 2009
  5. pmc The RhoA activator GEF-H1/Lfc is a transforming growth factor-beta target gene and effector that regulates alpha-smooth muscle actin expression and cell migration
    Anna Tsapara
    Department of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom
    Mol Biol Cell 21:860-70. 2010
  6. ncbi PAK4 mediates morphological changes through the regulation of GEF-H1
    Marinella G Callow
    SUGEN Incorporated, 230 East Grand Avenue, South San Francisco, CA 94080, USA
    J Cell Sci 118:1861-72. 2005
  7. ncbi Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers
    Logan C Walker
    Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, QLD, Australia
    Breast Cancer Res Treat 112:229-36. 2008
  8. ncbi Mutant p53 induces the GEF-H1 oncogene, a guanine nucleotide exchange factor-H1 for RhoA, resulting in accelerated cell proliferation in tumor cells
    Shinji Mizuarai
    Functional Genomics, Banyu Tsukuba Research Institute, Merck Research Laboratory, Tsukuba, Ibaraki, Japan
    Cancer Res 66:6319-26. 2006
  9. doi ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA
    Shuh Hei Fujishiro
    Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1 14, Bunkyo Machi, Nagasaki 852 8521, Japan
    Biochem Biophys Res Commun 368:162-7. 2008
  10. ncbi Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases
    Y Ren
    Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 273:34954-60. 1998

Detail Information

Publications204 found, 100 shown here

  1. pmc The epidermal growth factor receptor mediates tumor necrosis factor-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular epithelium
    Eli Kakiashvili
    Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael s Hospital, and Department of Surgery, University of Toronto, Toronto, Ontario M5B 1W8, Canada
    J Biol Chem 286:9268-79. 2011
    ..We have previously shown that ERK-mediated stimulation of the RhoA GDP/GTP exchange factor GEF-H1/Lfc is critical for TNF-α-induced RhoA stimulation...
  2. ncbi p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor
    Frank T Zenke
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 279:18392-400. 2004
    b>GEF-H1 is a guanine nucleotide exchange factor for Rho whose activity is regulated through a cycle of microtubule binding and release...
  3. pmc GEF-H1 couples nocodazole-induced microtubule disassembly to cell contractility via RhoA
    Yuan Chen Chang
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Mol Biol Cell 19:2147-53. 2008
    ..b>GEF-H1 is a microtubule-associated guanine nucleotide exchange factor that activates RhoA upon release from ..
  4. pmc Guanine nucleotide exchange factor-H1 regulates cell migration via localized activation of RhoA at the leading edge
    Perihan Nalbant
    Departments of Immunology and Microbial Science, and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Mol Biol Cell 20:4070-82. 2009
    ..The microtubule-associated guanine nucleotide exchange factor (GEF)-H1 activates RhoA when released from microtubules to initiate a RhoA/Rho kinase/myosin light chain signaling ..
  5. pmc The RhoA activator GEF-H1/Lfc is a transforming growth factor-beta target gene and effector that regulates alpha-smooth muscle actin expression and cell migration
    Anna Tsapara
    Department of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom
    Mol Biol Cell 21:860-70. 2010
    ..Here, we show that primary RPE cells up-regulated GEF-H1 in response to TGF-beta...
  6. ncbi PAK4 mediates morphological changes through the regulation of GEF-H1
    Marinella G Callow
    SUGEN Incorporated, 230 East Grand Avenue, South San Francisco, CA 94080, USA
    J Cell Sci 118:1861-72. 2005
    ..mediates morphological changes through its association with the Rho-family guanine nucleotide exchange factor (GEF), GEF-H1. We show that this association is dependent upon a novel GEF-H1 interaction domain (GID) within PAK4...
  7. ncbi Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers
    Logan C Walker
    Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, QLD, Australia
    Breast Cancer Res Treat 112:229-36. 2008
    ..Similar approaches may be used to identify genes and underlying genetic risk factors that interact with exogenous stimulants to cause or modify any disease, without a priori knowledge of the pathways involved...
  8. ncbi Mutant p53 induces the GEF-H1 oncogene, a guanine nucleotide exchange factor-H1 for RhoA, resulting in accelerated cell proliferation in tumor cells
    Shinji Mizuarai
    Functional Genomics, Banyu Tsukuba Research Institute, Merck Research Laboratory, Tsukuba, Ibaraki, Japan
    Cancer Res 66:6319-26. 2006
    ..In the present study, we showed that GEF-H1, a guanine exchange factor-H1 for RhoA, is transcriptionally activated by the induction of mutant p53 proteins, ..
  9. doi ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA
    Shuh Hei Fujishiro
    Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1 14, Bunkyo Machi, Nagasaki 852 8521, Japan
    Biochem Biophys Res Commun 368:162-7. 2008
    ..We have examined whether ERK1/2 are involved in the phosphorylation of GEF-H1, a GEF toward RhoA, to modulate its activity...
  10. ncbi Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases
    Y Ren
    Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 273:34954-60. 1998
    ..The Dbl-like guanine nucleotide exchange factors (GEF) have been implicated in direct activation of these GTPases...
  11. ncbi Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton
    Mira Krendel
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Nat Cell Biol 4:294-301. 2002
    ..Here we show that the Rho guanine nucleotide exchange factor (GEF)-H1 is regulated by an interaction with microtubules...
  12. pmc GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases
    Jörg Birkenfeld
    Departments of Immunology and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Dev Cell 12:699-712. 2007
    Formation of the mitotic cleavage furrow is dependent upon both microtubules and activity of the small GTPase RhoA. GEF-H1 is a microtubule-regulated exchange factor that couples microtubule dynamics to RhoA activation...
  13. ncbi Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition
    Saima Aijaz
    Division of Cell Biology, Institute of Ophthalmology, University College London, UK
    Dev Cell 8:777-86. 2005
    ..Here we show that GEF-H1/Lfc, a guanine nucleotide exchange factor for RhoA, directly interacts with cingulin, a junctional adaptor...
  14. pmc ARNO3, a Sec7-domain guanine nucleotide exchange factor for ADP ribosylation factor 1, is involved in the control of Golgi structure and function
    M Franco
    Centre d Immunologie Institut National de la Santé et de la Recherche Médicale Centre National de la Recherche Scientifique de Marseille Luminy, Case 906, 13288 Marseille Cedex 9, France
    Proc Natl Acad Sci U S A 95:9926-31. 1998
    ..We recently have identified a human protein, ARNO (ARF nucleotide-binding-site opener), as an ARF1-GEF that shares a conserved domain with the yeast Sec7 protein...
  15. ncbi Antagonistic effects of NES and NLS motifs determine S. cerevisiae Rna1p subcellular distribution
    W Feng
    Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Cell Sci 112:339-47. 1999
    ..In yeast Rna1p is the GTPase activating protein for Ran (RanGAP) and Prp20p is the Ran GDP/GTP exchange factor (GEF). RanGAP is primarily cytosolic and GEF is nuclear...
  16. pmc Perturbations in the spi1p GTPase cycle of Schizosaccharomyces pombe through its GTPase-activating protein and guanine nucleotide exchange factor components result in similar phenotypic consequences
    A Matynia
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 16:6352-62. 1996
    ..products, rna1p and pim1p, functioning as GTPase-activating protein (GAP) and guanine nucleotide exchange factor (GEF), respectively...
  17. ncbi RCC1 in the Ran pathway
    T Seki
    Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka
    J Biochem 120:207-14. 1996
    RCC1 is a chromosomal protein that functions as a GEF of the nuclear G protein Ran, which GTPase activity is enhanced by RNA1 located in the cytoplasm...
  18. ncbi Quantitative morphology and postsynaptic targets of thalamocortical axons in critical period and adult ferret visual cortex
    Alev Erisir
    University of Virginia, Department of Psychology, Charlottesville, Virginia 22904 4400, USA
    J Comp Neurol 485:11-31. 2005
    ..anterograde tract-tracing display significantly larger cross-section areas than terminals at postnatal day (P) 35, P40, and P49 critical period ages...
  19. ncbi Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras
    X Gao
    Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Japan
    J Biol Chem 276:42219-25. 2001
    ..RA-GEF-1 was identified as a novel Rap GEF, which possesses a Ras/Rap1-associating (RA) domain...
  20. ncbi Interaction between 3' untranslated region of calcitonin receptor messenger ribonucleic acid (RNA) and adenylate/uridylate (AU)-rich element binding proteins (AU-rich RNA-binding factor 1 and Hu antigen R)
    Shigemitsu Yasuda
    Fourth Department of Internal Medicine, Saitama Medical School, Japan
    Endocrinology 145:1730-8. 2004
    ..3'UTR transcripts bound with a 40-kDa protein, which could be extracted from cells transfected with AUF1 p40. To confirm the binding specificity, a pSG5 vector construct, containing the AUF1 p40 with an hemagglutinin tag, ..
  21. pmc Measles virus N protein inhibits host translation by binding to eIF3-p40
    Hiroki Sato
    Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Virol 81:11569-76. 2007
    ..by using MV-N as bait and screening the human T-cell cDNA library by yeast two-hybrid assay and isolated the p40 subunit of eukaryotic initiation factor 3 (eIF3-p40) as a binding partner...
  22. pmc Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis
    K Shigehara
    First Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
    Clin Exp Immunol 132:152-7. 2003
    ..The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was ..
  23. ncbi Spinal dural arteriovenous malformations. Intraoperative evoked potential evidence for pathophysiology. A case report
    M M Stecker
    Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
    Spine (Phila Pa 1976) 21:512-5. 1996
    ..RESULTS. At baseline, the cortical (P40) potential was markedly prolonged bilaterally...
  24. ncbi Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist
    S Gillessen
    Department of Inflammation Autoimmune Diseases, Hoffmann La Roche Inc, Nutley, NJ 07110
    Eur J Immunol 25:200-6. 1995
    ..that has regulatory effects on T and natural killer (NK) cells and is composed of two disulfide-bonded subunits, p40 and p35...
  25. pmc In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70
    Karen L Elkins
    Laboratory of Mycobacteria, Division of Bacterial, Parasitic, and Allergenic Products, CBER FDA, Rockville, Maryland 20852, USA
    Infect Immun 70:1936-48. 2002
    ..Mice lacking the p40 protein of IL-12 (p40 knockout [KO] mice) and mice treated in vivo with neutralizing anti-IL-12 antibodies survived ..
  26. ncbi Effects of stimulus intensity and duration on posterior tibial nerve somatosensory-evoked potential patterns obtained under anesthesia
    M Rappaport
    University of California Brain Function Study Unit, Agnews Developmental Center, San Jose
    Spine (Phila Pa 1976) 19:1525-9. 1994
    ..RESULTS. Three latencies yielded stable findings (P40, N50, P60). Peak latencies under anesthesia were not affected by stimulus intensity or duration...
  27. pmc Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians
    Nicole G Hunfeld
    Central Hospital Pharmacy, The Hague, The Netherlands
    Br J Clin Pharmacol 65:752-60. 2008
    ..Furthermore, a novel CYP2C19 mutation, *17, which mainly occurs in Caucasians has been discovered. This mutation has been associated with clinical failure, but its relevance for therapy with PPIs has not been studied yet...
  28. pmc Role of Mycoplasma penetrans endonuclease P40 as a potential pathogenic determinant
    M Bendjennat
    Laboratory of Immunovirology UFR SVT, University of Paul Sabatier, 31062 Toulouse, France
    Infect Immun 67:4456-62. 1999
    ..we reported the purification to homogeneity and characterization of Ca(2+)- and Mg(2+)-dependent endonuclease P40 produced by Mycoplasma penetrans (M. Bendjennat, A. Blanchard, M. Loutfi, L. Montagnier, and E. Bahraoui, J...
  29. ncbi Complementation of NADPH oxidase in p67-phox-deficient CGD patients p67-phox/p40-phox interaction
    S Vergnaud
    GREPI, Laboratoire d Enzymologie, CHU, Grenoble, France INSERM U 479, CHU, Bichat, Paris, France
    Eur J Biochem 267:1059-67. 2000
    ..b558 that was associated with cytosol or with the isolated cytosolic-activating factors (p67-phox, p47-phox, p40-phox) from healthy or CGD patients...
  30. ncbi IL-12 and IFN-gamma production, and NK cell activity, in acute and chronic experimental Trypanosoma cruzi infections
    M I Antunez
    Instituto Nacional de Parasitologia Dr M Fatala Chaben, ANLIS Dr C G Malbran, Buenos Aires, Argentina
    Immunol Lett 71:103-9. 2000
    ..cruzi, Tulahuén strain was studied. The levels of interleukin-12 p40 (IL-12 p40) and IFN-gamma, as well as natural killer (NK) cell cytotoxicity were determined at different time-..
  31. pmc Lack of interleukin-12 in p40-deficient mice leads to poor CD8+ T-cell immunity against Encephalitozoon cuniculi infection
    Magali M Moretto
    Department of Microbiology, George Washington University, 2300 I Street, Washington, DC 20037, USA
    Infect Immun 78:2505-11. 2010
    ..In the present study, we demonstrated that p40-deficient animals, which are unable to produce interleukin-12 (IL-12), have a serious defect in expansion of the ..
  32. pmc Eukaryotic initiation factor 2B (eIF2B) GEF activity as a diagnostic tool for EIF2B-related disorders
    Laetitia Horzinski
    INSERM U931 CNRS 6247 Université Clermont, GReD, Clermont Ferrand, France
    PLoS ONE 4:e8318. 2009
    ..Decreased eIF2B GEF activity has been previously reported in lymphoblastoid cell lines from 30 eIF2B-mutated patients...
  33. ncbi Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity
    P Ling
    Department of Inflammation Autoimmune Diseases, Hoffmann La Roche, Inc, Nutley, NJ 07110
    J Immunol 154:116-27. 1995
    IL-12, a heterodimeric cytokine, consists of two disulfide-linked subunits, p40 and p35. We investigated the role of p40 in ligand binding and signal transduction by expressing this subunit alone in COS cells...
  34. ncbi Modulation of IL-12 p35 and p40 promoter activity by smokeless tobacco extract is associated with an effect upon activation of NF-kappaB but not IRF transcription factors
    Thomas M Petro
    Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, 40th and Holdrege Streets, Lincoln, NE 68583 0740, USA
    Int Immunopharmacol 3:735-45. 2003
    Interleukin (IL)-12 (p70), composed of p35 and p40 subunits, stimulates cellular immunity and inflammation. Stimulation of IL-12 production by smokeless tobacco extract (STE) could increase the chances of oral inflammatory disease...
  35. pmc Dual system to reinforce biological containment of recombinant bacteria designed for rhizoremediation
    M C Ronchel
    Department of Biochemistry and Molecular and Cellular Biology of Plants, Estacion Experimental del Zaidin, Consejo Superior de Investigaciones Cientificas, 18008 Granada, Spain
    Appl Environ Microbiol 67:2649-56. 2001
    ..g., a porin-inducing protein such as the one encoded by the Escherichia coli gef gene, and a regulatory circuit that controls expression of the killing gene in response to the presence or absence ..
  36. pmc The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells
    X Ma
    Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104, USA
    J Exp Med 183:147-57. 1996
    ..IL-12 production mostly by priming phagocytic cells for lipopolysaccharide (LPS)-induced transcription of the IL-12 p40 gene, which encodes the heavy chain of the IL-12 heterodimer; furthermore, IFN-gamma directly induces transcription ..
  37. pmc PEST-dependent cytoplasmic retention of v-Rel by I(kappa)B-alpha: evidence that I(kappa)B-alpha regulates cellular localization of c-Rel and v-Rel by distinct mechanisms
    E M Rottjakob
    Department of Biochemistry, University of Missouri, Columbia 65212, USA
    J Virol 70:3176-88. 1996
    ..The ability of v-Rel, the oncogenic viral counterpart of avian c-Rel, to evade regulation by p40, the avian IkappaB-alpha protein, contributes to v-Rel-mediated oncogenesis...
  38. pmc Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells
    A D'ANDREA
    Wistar Institute of Anatomy and Biology, Children s Hospital of Philadelphia, Pennsylvania 19104
    J Exp Med 176:1387-98. 1992
    ..NKSF), or interleukin 12 (IL-12), is a 70-kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35...
  39. ncbi Estimation of left ventricular systolic function by single transpulmonary thermodilution
    Alain Combes
    Service de Reanimation Medicale, Hopital Pitie Salpetriere, Assistance Publique Hopitaux de Paris, 47, Boulevard de l Hopital, 75651 Paris Cedex 13, France
    Intensive Care Med 30:1377-83. 2004
    ..The global cardiac systolic function may be decreased despite preserved left ventricular function in this situation.)..
  40. 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
    PDZ-GEF is a novel guanine nucleotide exchange factor for Rap1 GTPase...
  41. ncbi Characterization and localized expression of the laminin binding protein/p40 (LBP/p40) gene during sea urchin development
    M Hung
    Department of Biological Sciences, California State University, Hayward 94542, USA
    Exp Cell Res 221:221-30. 1995
    ..of a cDNA clone from the sea urchin Strongylocentrotus purpuratus that encodes a protein very similar to LBP/p40, originally identified as a nonintegrin, 67-kDa laminin binding protein...
  42. ncbi Induction of rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) following phosphorylation by the nonreceptor tyrosine kinase Src
    M Kiyono
    Faculty of Bioscience, Tokyo Institute of Technology, Yokohama 226 8501, Japan
    J Biol Chem 275:5441-6. 2000
    Ras-GRF1/CDC25(Mm) has been implicated as a Ras-guanine nucleotide exchange factor (GEF) expressed in brain. Ras-GEF activity of Ras-GRF1 is augmented in response to Ca(2+) influx and G protein betagamma subunit (Gbetagamma) stimulation...
  43. ncbi Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells
    S F Wolf
    Genetics Institute, Inc, Cambridge, MA 02140
    J Immunol 146:3074-81. 1991
    ..NKSF was found to be a disulfide-linked heterodimeric protein composed of 35-kDa and 40-kDa subunits (p35 and p40). We now report the molecular cloning of cDNA for both subunits of NKSF from RPMI 8866 cellular RNA...
  44. 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
    ..for Ras-binding proteins in nematode Caenorhabditis elegans has identified a guanine nucleotide exchange factor (GEF) containing a Ras/Rap1A-associating (RA) domain, termed Ce-RA-GEF...
  45. ncbi Expression of the guanine nucleotide exchange factor, mr-gef, is regulated during the differentiation of specific subsets of telencephalic neurons
    Angela Bithell
    Section of Experimental Neuropathology and Psychiatry, Department of Psychological Medicine, The Institute of Psychiatry P052, De Crespigny Park, London SE5 8AF, UK
    Brain Res Dev Brain Res 146:107-18. 2003
    ..Here we report that one of these genes, encoding a guanine nucleotide exchange factor (GEF), is regulated during the differentiation of distinct neuronal populations...
  46. ncbi betaPak-interacting exchange factor-mediated Rac1 activation requires smgGDS guanine nucleotide exchange factor in basic fibroblast growth factor-induced neurite outgrowth
    Eun Young Shin
    Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju 361 763, Korea
    J Biol Chem 281:35954-64. 2006
    ..1994-2004), we demonstrated that betaPak-interacting exchange factor (betaPIX) guanine nucleotide exchange factor (GEF) mediates basic fibroblast growth factor (bFGF)-stimulated Rac1 activation through phosphorylation of Ser-525 and ..
  47. ncbi Exhaustive exercise and type-1/type-2 cytokine balance with special focus on interleukin-12 p40/p70
    Katsuhiko Suzuki
    Department of Hygiene, Hirosaki University School of Medicine, Aomori, Japan
    Exerc Immunol Rev 9:48-57. 2003
    ..produce type-1 cytokines such as IL-2 and interferon (IFN), thereby supporting cellular immunity, whereas IL-12 p40 acts as an antagonist of IL-12 p70...
  48. ncbi Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1
    M Kiyono
    Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226 8501, Japan
    J Biol Chem 275:29788-93. 2000
    Ras-GRF1 is a brain-specific guanine nucleotide exchange factor (GEF) for Ras, whose activity is regulated in response to Ca(2+) influx and G protein-coupled receptor signals...
  49. pmc The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains
    A Debant
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:5466-71. 1996
    ..isolated a cDNA encoding a 2861-amino acid protein termed Trio that contains three enzyme domains: two functional GEF domains and a protein serine/threonine kinase (PSK) domain...
  50. doi The role of the conserved switch II glutamate in guanine nucleotide exchange factor-mediated nucleotide exchange of GTP-binding proteins
    Raphael Gasper
    Abteilung Strukturelle Biologie, Max Planck Institut fur molekulare Physiologie, 44227 Dortmund, Germany
    J Mol Biol 379:51-63. 2008
    ..The mechanism involves the formation of trimeric G protein-nucleotide-GEF complexes, followed by the release of nucleotide to form stable binary G protein-GEF complexes...
  51. ncbi Induction of lamellipodia by Kalirin does not require its guanine nucleotide exchange factor activity
    Martin R Schiller
    Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030 3401, USA
    Exp Cell Res 307:402-17. 2005
    Guanine nucleotide exchange factor (GEF) domains of the Dbl family occur in a variety of proteins that include multiple protein-protein and protein-lipid interaction domains...
  52. ncbi Specific recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 guanine nucleotide exchange factors
    Michael A Kwofie
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    J Biol Chem 283:3088-96. 2008
    Recognition of cognate Rho GTPases by guanine-nucleotide exchange factors (GEF) is fundamental to Rho GTPase signaling specificity...
  53. pmc cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 beta/alpha in rat hepatocytes
    Anna Gates
    Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536, USA
    Am J Physiol Gastrointest Liver Physiol 296:G764-74. 2009
    Cyclic AMP protects against hepatocyte apoptosis by a protein kinase A-independent cAMP-GEF/phosphoinositide-3-kinase (PI3K)/Akt signaling pathway. However, the signaling pathway coupling cAMP-GEF with PI3K is unknown...
  54. pmc Guanine nucleotide exchange factor independence of the G-protein eEF1A through novel mutant forms and biochemical properties
    Sedide B Ozturk
    Department of Molecular Genetics, Microbiology, and Immunology, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA
    J Biol Chem 283:23244-53. 2008
    Most G-proteins require a guanine nucleotide exchange factor (GEF) to regulate a variety of critical cellular processes. Interestingly, a small number of G-proteins switch between the active and inactive forms without a GEF...
  55. ncbi Inhibitors of ATP-binding cassette transporters suppress interleukin-12 p40 production and major histocompatibility complex II up-regulation in macrophages
    Gyorgy Hasko
    Department of Surgery, University of Medicine and Dentistry New Jersey Medical School, Newark, New Jersey 07103, USA
    J Pharmacol Exp Ther 301:103-10. 2002
    ..in the regulation of lipopolysaccharide (LPS) and/or interferon (IFN)-gamma-induced interleukin (IL)-12 p40 and tumor necrosis factor (TNF)-alpha production, nitric oxide formation, as well as major histocompatibility ..
  56. pmc Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder
    Angela Bithell
    Department of Psychological Medicine, Institute of Psychiatry, King s College London, London, United Kingdom
    PLoS ONE 5:e10392. 2010
    ..The Rap-1 guanine nucleotide exchange factor, MR-GEF, is turned on by many of these developing GABAergic neurons...
  57. pmc Heparin inhibits pulmonary artery smooth muscle cell proliferation through guanine nucleotide exchange factor-H1/RhoA/Rho kinase/p27
    Lunyin Yu
    Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 2696, USA
    Am J Respir Cell Mol Biol 44:524-30. 2011
    ..We also investigated the effect of guanine nucleotide exchange factor (GEF)-H1, an upstream regulator of RhoA, on heparin inhibition of PASMC proliferation by GEF-H1 cDNA transfection...
  58. pmc Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity
    D Dailey
    Department of Molecular and Cell Biology, University of California, Berkeley 94720
    Mol Cell Biol 10:6244-56. 1990
    ..level of tyrosine kinase activity at all steps of each preparation correlated with the content of a 40-kDa protein (p40)...
  59. ncbi Protective immunity induced with 23 kDa membrane protein dna vaccine of Schistosoma japonicum Chinese strain in infected C57BL/6 mice
    Yingchang Zhu
    Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, PR China
    Southeast Asian J Trop Med Public Health 34:697-701. 2003
    ..m.) with a mixture of 100 microg of pcDNA3.1-SjC23, 100 microg of pcDNA3.1-p35 and 100 microg of pcDNA-p40. These were followed by two boosts of the same DNA once every two weeks...
  60. ncbi Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes
    M P Hayes
    Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892, USA
    Blood 86:646-50. 1995
    ..factor (GM-CSF) provided an equivalent priming stimulus for LPS-induced tumor necrosis factor (TNF) and IL-12 p40 mRNA, but primed poorly for LPS-inducible p35 message and secreted IL-12 activity...
  61. ncbi Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients
    Tomomi Toubai
    Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Eur J Haematol 77:403-9. 2006
    Interleukin (IL)-12 is a 70-kDa cytokine comprised of two disulfide-linked proteins (p35 and p40) and is essential for the initiation of effective immune response...
  62. ncbi Characterization of p40 and IL-10 in the BALF of patients with pulmonary sarcoidosis
    Virginie Barbarin
    Industrial Toxicology and Occupational Medicine Unit, Universite Catholique de Louvain, Brussels, Belgium
    J Interferon Cytokine Res 23:449-56. 2003
    This study investigated cytokine protein levels (interleukin-12 p70 [IL-12p70], p40, and IL-10) in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis (n = 59), healthy control subjects (n = 17), and patients ..
  63. pmc Induction of tumor necrosis factor-alpha (TNF-alpha) by interleukin-12 p40 monomer and homodimer in microglia and macrophages
    Malabendu Jana
    Department of Oral Biology, University of Nebraska Medical Center, Lincoln, Nebraska 68583 0740, USA
    J Neurochem 86:519-28. 2003
    The present study was undertaken to explore the role of interleukin-12 (IL-12) p40 in the expression of TNF-alpha in microglia...
  64. ncbi Do subplate neurons comprise a transient population of cells in developing neocortex of rats?
    R T Robertson
    Department of Anatomy and Neurobiology, College of Medicine, University of California, Irvine, California 92697 1280, USA
    J Comp Neurol 426:632-50. 2000
    ..dissector method was used to analyze fluorescently stained material in animals the age of postnatal day 0 (P0) to P40. These results demonstrate a reduction of slightly less than half of the total number of subplate neurons from P0 ..
  65. pmc Induction of lymphotoxin-alpha by interleukin-12 p40 homodimer, the so-called biologically inactive molecule, but not IL-12 p70
    Malabendu Jana
    Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA
    Immunology 127:312-25. 2009
    Interleukin-12 (IL-12) p70 (p40:p35) is a bioactive cytokine and its biological functions are becoming clear...
  66. doi Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study
    Benjamin M Segal
    Department of Neurology, Holtom Garrett Programme in Neuroimmunology, University of Michigan, Ann Arbor, MI 48109 2200, USA
    Lancet Neurol 7:796-804. 2008
    Repeated subcutaneous injections of a monoclonal antibody against the p40 subunit of interleukins 12 and 23, ustekinumab, were used to treat patients with relapsing-remitting multiple sclerosis (RRMS) to assess the drug's safety, ..
  67. ncbi Ovarian follicular concentration of IL-12, IL-15, IL-18 and p40 subunit of IL-12 and IL-23
    Sanja Vujisic
    Department of Obstetrics and Gynecology, Medical School, University of Zagreb, Sveti Duh Hospital, Croatia
    Hum Reprod 21:2650-5. 2006
    The aim of the study was to determine the presence of interleukin (IL)-12, IL-15, IL-18 and p40 subunit of IL-12/IL-23 in follicular fluid from spontaneous cycles and the relation between the concentration of selected cytokines and IVF-..
  68. ncbi Generation of an active protein-tyrosine kinase from lymphocytes by proteolysis
    T F Zioncheck
    Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907
    J Biol Chem 263:19195-202. 1988
    ..found in soluble thymus extracts, as measured by the phosphorylation of angiotensin I, is a 40-kDa enzyme known as p40 (Zioncheck, T. F., Harrison, M. L., and Geahlen, R. L. (1986) J. Biol. Chem. 261, 15637-15643)...
  69. ncbi Copper induces the assembly of a multiprotein aggregate implicated in the release of fibroblast growth factor 1 in response to stress
    M Landriscina
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA
    J Biol Chem 276:25549-57. 2001
    ..is known to be released in response to stress conditions as a component of a multiprotein aggregate containing the p40 extravescicular domain of p65 synaptotagmin (Syt) 1 and S100A13...
  70. ncbi Nitric oxide inhibits interleukin-12 p40 through p38 MAPK-mediated regulation of calmodulin and c-rel
    Chandra Sekhar Boddupalli
    Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, ECIL Road, Nacharam, Hyderabad 500076, Andhra Pradesh, India
    Free Radic Biol Med 42:686-97. 2007
    ..macrophages, the rel/NF-kappaB transcription factors are known to play important roles in interleukin-12 (IL-12) p40 regulation by nitric oxide (NO). However, the relative contributions of these factors are not well understood...
  71. ncbi Accumulation of processing intermediates of the RAS2 protein in strain 112 of Saccharomyces cerevisiae
    D Breviario
    Istituto Tecnologie Biomediche Avanzate, CNR, Milano, Italy
    Biochem Biophys Res Commun 151:1346-51. 1988
    ..molecule of 41000 daltons (p41), 112 cells accumulate within the soluble fraction an intermediate form of RAS2 (p40-1), which migrates, in SDS-polyacrylamide gel, between p41 and the fully processed, membrane-bound 40,000 daltons (..
  72. pmc NCAM180 regulates Ric8A membrane localization and potentiates β-adrenergic response
    Marie Claude Amoureux
    Institut de Biologie du Developpement de Marseille Luminy, Aix Marseille Université CNRS 6216, Marseille, France
    PLoS ONE 7:e32216. 2012
    ..we show that the human NCAM180 intracellular domain is a novel interactor of the human guanosine exchange factor (GEF) Ric8A using the yeast two hybrid system and immunoprecipitation...
  73. doi Leprosy and pregnancy: detection coefficient and proposal for a new index
    Vera Regina da Cunha Menezes Palácios
    Departamento de Saude Comunitaria, Universidade do Estado do Pará, Belem, PA, Brazil
    Rev Soc Bras Med Trop 47:798-800. 2014
    ..Data were ordered, divided into five equal parts (corresponding to the P20, P40, P60, and P80 percentiles), and classified as low, medium, high, very high, or hyperendemic.
  74. pmc Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro
    Partha Mukhopadhyay
    Section on Oxidative Stress and Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, MSC 9413, Bethesda, MD 20892 9413, USA
    Am J Physiol Heart Circ Physiol 296:H1466-83. 2009
    ..polymerase activation [without major changes in NAD(P)H oxidase isoform 1, NAD(P)H oxidase isoform 2, p22(phox), p40(phox), p47(phox), p67(phox), xanthine oxidase, endothelial NOS, and neuronal NOS expression] and decreases in ..
  75. pmc Triptolide inhibits IL-12/IL-23 expression in APCs via CCAAT/enhancer-binding protein alpha
    Yan Zhang
    Department of Microbiology and Immunology, Weill Medical College, eill Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA
    J Immunol 184:3866-77. 2010
    ..IL-12 and IL-23 are closely related heterodimeric cytokines that share the common subunit p40. They are produced by APCs and are key factors in the generation and effector functions of Th1 and Th17 cells, ..
  76. pmc Tobacco-induced alterations to Porphyromonas gingivalis-host interactions
    Juhi Bagaitkar
    Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA
    Environ Microbiol 11:1242-53. 2009
    ..extract (CSE) induce a lower proinflammatory response (tumour necrosis factor-alpha, interleukin-6, interleukin-12 p40) from monocytes and peripheral blood mononuclear cells than do unexposed bacteria...
  77. pmc Interaction between the type III effector VopO and GEF-H1 activates the RhoA-ROCK pathway
    Hirotaka Hiyoshi
    Laboratory of Genomic Research on Pathogenic Bacteria, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
    PLoS Pathog 11:e1004694. 2015
    ..We also determined that GEF-H1, a RhoA guanine nucleotide exchange factor (GEF), directly binds VopO and is necessary for T3SS2-dependent ..
  78. doi Pathogenic mechanisms and experimental models of multiple sclerosis
    Anthony Slavin
    Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT 06887, USA
    Autoimmunity 43:504-13. 2010
    ..mechanisms that have worked in EAE but have failed in the clinic, such as the TNFα antagonists and anti-p40 (a subunit of IL-12 and IL-23)...
  79. ncbi Toll-like receptor 2 mediates inflammatory cytokine induction but not sensitization for liver injury by Propioni- bacterium acnes
    Laszlo Romics
    Liver Center, Department of Medicine, University of Massachusetts Medical School, LRB 215, 364 Plantation Street, Worcester, MA 01605 2324, USA
    J Leukoc Biol 78:1255-64. 2005
    ..levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, interferon-gamma (IFN-gamma), and IL-12 (p40/p70), and increased RNA expression of proinflammatory cytokines (IL-12p40, IL-1alpha, IL-6, IL-1beta, IL-18, IFN-..
  80. doi Sequential application of chelating agents and innovative surfactants for the enhanced electroremediation of real sediments from toxic metals and PAHs
    John N Hahladakis
    School of Environmental Engineering, Technical University of Crete, Politechnioupolis, Chania 73100, Greece Electronic address
    Chemosphere 105:44-52. 2014
    ..the efficiency evaluation of two innovative non-ionic surfactants, commercially known as Poloxamer 407 and Nonidet P40, was investigated...
  81. ncbi Role of interleukin 12 in hypercholesterolemia-induced inflammation
    Karen Y Stokes
    Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 E Kings Highway, Shreveport, LA 71130 3932, USA
    Am J Physiol Heart Circ Physiol 285:H2623-9. 2003
    ..C57Bl/6, lymphocyte-deficient [recombinase-activating gene knockout (RAG1-/-)], and IL-12-deficient (p35-/- and p40-/-; p35 and p40 are the two subunits of active IL-12) mice on either a normal (ND) or high-cholesterol (HC) diet ..
  82. pmc IL-12 Promotes Myeloid-Derived Suppressor Cell Recruitment and Bacterial Persistence during Staphylococcus aureus Orthopedic Implant Infection
    Cortney E Heim
    Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198 and
    J Immunol 194:3861-72. 2015
    ..particular interest based on its ability to possess either pro- or anti-inflammatory effects mediated through p35-p40 heterodimers or p40 homodimers, respectively...
  83. ncbi mRNA transfection of a novel TAL effector nuclease (TALEN) facilitates efficient knockout of HIV co-receptor CCR5
    Ulrike Mock
    Research Dept Cell and Gene Therapy, Dept of Stem cell Transplantation, University Medical Centre Hamburg Eppendorf UKE, Hamburg, 20246, Germany
    Nucleic Acids Res . 2015
    ..flow cytometry, next-generation sequencing and a newly devised, very convenient gene-editing frequency digital-PCR (GEF-dPCR)...
  84. doi Nitrated fatty acids prevent TNFalpha-stimulated inflammatory and atherogenic responses in endothelial cells
    Jinah Hwang
    Department of Food and Nutrition, Myongji University, Yongin, Republic of Korea
    Biochem Biophys Res Commun 387:633-40. 2009
    ..Both OA-NO(2) and LNO(2) prevented TNFalpha-stimulated release of the cytokines, IL-6, IL-8, IL-12/p40, IFNgamma, MCP-1, and IP-10, and inhibited NF-kappaB activation...
  85. pmc Remedial strategies in structural proteomics: expression, purification, and crystallization of the Vav1/Rac1 complex
    Alexei Brooun
    Department of Cellular Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, MB 201, La Jolla, CA 92037, USA
    Protein Expr Purif 53:51-62. 2007
    The signal transduction pathway involving the Vav1 guanine nucleotide exchange factor (GEF) and the Rac1 GTPase plays several key roles in the immune response mediated by the T cell receptor...
  86. doi The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7
    Mirjana Nordmann
    Department of Biology Chemistry, University of Osnabruck, Germany
    Curr Biol 20:1654-9. 2010
    Rab GTPases coordinate membrane fusion reactions [1]. Rab-GDP requires a guanine nucleotide exchange factor (GEF) for its conversion to the active GTP form...
  87. pmc The ataxia telangiectasia mutated kinase pathway regulates IL-23 expression by human dendritic cells
    Qunwei Wang
    Host Tumour Interactions Group, Academic Unit of Clinical Oncology, University of Nottingham, Nottingham NG5 1PB, United Kingdom
    J Immunol 190:3246-55. 2013
    ..Although ATM blockade increased the abundance of p19, p35, and p40 mRNA, IL-12p70 secretion was unaffected...
  88. ncbi [Determination of the cytokine gene polymorphism and genetic susceptibility in tuberculosis patients]
    Mahmut Ulger
    Department of Medical Microbiology, Mersin University Faculty of Medicine, Mersin, Turkey
    Mikrobiyol Bul 47:250-64. 2013
    ..G>A (rs1800629) region, interferon gamma (IFN-γ) gene +874 T>A (rs61923114) region, interleukin (IL)-12B p40 gene 1188 A>C (rs3212227) region, IL-10 gene promoter -1082 G>A (rs1800896) region and IL-4 gene promoter -..
  89. doi RNA-aptamers that modulate the RhoGEF activity of Tiam1
    Björn Niebel
    Life and Medical Sciences LIMES Institute, University of Bonn, Gerhard Domagk Str 1, 53121 Bonn, Germany
    Bioorg Med Chem 21:6239-46. 2013
    ..The gene product of the oncogene Tiam1 acts as a guanine nucleotide exchange factor (GEF) for the Rho GTPase Rac...
  90. pmc S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation
    Joseph E Aslan
    Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA
    Blood 118:3129-36. 2011
    ..S6K1 and Rac1 interacted in a protein complex with the Rac1 GEF TIAM1 and colocalized with actin at the platelet lamellipodial edge, suggesting that S6K1 and Rac1 work together to ..
  91. doi The (R)-enantiomer of CE3F4 is a preferential inhibitor of human exchange protein directly activated by cyclic AMP isoform 1 (Epac1)
    Delphine Courilleau
    Univ Paris Sud, CIBLOT IFR 141, Faculte de Pharmacie, 92296 Chatenay Malabry Cedex, France
    Biochem Biophys Res Commun 440:443-8. 2013
    ..Their guanine-nucleotide exchange factor (GEF) activity toward the small GTP-binding protein Rap1 is stimulated by the agonist cAMP...
  92. pmc The spindle pole bodies facilitate nuclear envelope division during closed mitosis in fission yeast
    Liling Zheng
    Cell Dynamics Group, Temasek Life Sciences Laboratory, Singapore
    PLoS Biol 5:e170. 2007
    ..Strikingly, when the NE was disassembled by utilizing a temperature-sensitive allele of the Ran GEF, Pim1p, the abnormal spindles induced by Mia1p overexpression were capable of segregating sister chromatids to ..
  93. 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
    ..disengagement activated Rap1 and this correlated with E-cadherin association with the Rap GEFs, C3G and PDZ-GEF I...
  94. doi C-terminal motif within Sec7 domain regulates guanine nucleotide exchange activity via tuning protein conformation
    Biao Qiu
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China Graduate School of the Chinese Academy of Sciences, Beijing 100049, China
    Biochem Biophys Res Commun 446:380-6. 2014
    ..yeast trans-Golgi network membrane localized Arf-GEFs, and found that the loop>J motif is indispensible for its GEF catalytic activity...
  95. pmc Coordination of Golgi functions by phosphatidylinositol 4-kinases
    Todd R Graham
    Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA
    Trends Cell Biol 21:113-21. 2011
    ..include Vps74/GOLPH3, a phospholipid flippase called Drs2 and Sec2, a Rab guanine nucleotide exchange factor (GEF). These effectors orchestrate membrane transformation events facilitating vesicle formation and targeting...
  96. ncbi Asymmetric coiled-coil structure with Guanine nucleotide exchange activity
    Yusuke Sato
    Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta cho, Yokohama shi, Kanagawa, Japan
    Structure 15:245-52. 2007
    ..exocytosis is regulated by Rab GTPase, Sec4p in yeast, which is activated by a guanine nucleotide exchange factor (GEF) called Sec2p...
  97. pmc Frabin and other related Cdc42-specific guanine nucleotide exchange factors couple the actin cytoskeleton with the plasma membrane
    Hiroyuki Nakanishi
    Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    J Cell Mol Med 12:1169-76. 2008
    Frabin, together with, at least, FGD1, FGD2, FGD3 and FGD1-related Cdc42-GEF (FRG), is a member of a family of Cdc42-specific gua-nine nucleotide exchange factors (GEFs)...
  98. doi P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils
    George Damoulakis
    Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK
    J Cell Sci 127:2589-600. 2014
    ..The guanine-nucleotide-exchange factor (GEF) P-Rex1 is engaged downstream of GPCRs and phosphoinositide 3-kinase (PI3K) in many cell types, and promotes ..
  99. doi p100, a precursor of NF-κB2, inhibits c-Rel and reduces the expression of IL-23 in dendritic cells
    Setsuko Mise-Omata
    Technology and Development Team for BioSignal Program, Subteam for BioSignal Integration, RIKEN BioResource Center, RIKEN Tsukuba Institute, 3 1 1 Koyadai, Tsukuba 305 0074, Japan Electronic address
    Biochem Biophys Res Commun 453:332-7. 2014
    ..Here, we demonstrate that p100 also suppresses c-Rel function in dendritic cells. Expression of the p19 and p40 subunits of IL-23, a c-Rel-dependent cytokine, was enhanced in p100-deficient cells, although expression of a RelA-..
  100. ncbi PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis
    Susumu Seino
    Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Physiol Rev 85:1303-42. 2005
    ..Newly discovered cAMP-GEF/Epac, which belongs to the cAMP-binding protein family, exhibits guanine nucleotide exchange factor activities and ..
  101. ncbi Distinct contributions of different CD40 TRAF binding sites to CD154-induced dendritic cell maturation and IL-12 secretion
    Matthew F Mackey
    Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1892, Bethesda, MD 20892 1892, USA
    Eur J Immunol 33:779-89. 2003
    ..In contrast, disruption of the TRAF6 but not the TRAF 2,3,5 binding site markedly decreased IL-12 p40 secretion along with p38 and JNK activation in response to CD154 stimulation...

Research Grants65

  1. ACTIVATION OF NF-KB IN GLIAL CELLS AND CNS OF EAE
    Kalipada Pahan; Fiscal Year: 2009
    ..We have discovered a new group of inducers of NF-kappaB activation [interleukin-12 (IL-12) p40 homodimer (p40-2) and monomer (p40)] in glial cells. It was known that p40-2 and p40 were biologically inactive...
  2. Anti-IL-12p40 Treatment of CVID Enteropathy: Gene Expression/Microbiota Analysis
    Warren Strober; Fiscal Year: 2013
    ..Ustekinumab is a monoclonal antibody to the p40 subunit of interleukin-12/23...
  3. Opposing Mechanisms of Stabilizing and Destabilizing Receptors
    DEAN YAW LI; Fiscal Year: 2013
    ..are due to the activation of opposing GTPase activating proteins (GAP) and guanine nucleotide exchange factors (GEF) that determine, respectively, the inactive and active state of ARF6 and the strength of cell-cell interactions...
  4. Rac GTPase-Specific Small Molecular Inhibitors
    Yi Zheng; Fiscal Year: 2013
    ..The GEF-Rac signaling axis lies in the crossroads of many signaling events initiated by growth factors, cytokines, stress, ..
  5. Diverse Roles for RIC8 During G Protein Signaling in Fungi
    Katherine A Borkovich; Fiscal Year: 2012
    ..Loss of ric8 leads to reduced levels of G proteins in Drosophila, suggesting a chaperone function in addition to GEF activity. RIC8 is absent from plants, protists and the yeast Saccharomyces cerevisiae...
  6. MOLECULAR REGULATION OF INTERLEUKIN 12 GENE EXPRESSION
    Xiaojing Ma; Fiscal Year: 2003
    ..IL-12 is a heterodimer consisted to two subunits, p40 and p35 that are encoded on different human chromosomes...
  7. Pairing of EBI-3 and IL12 p35 To Yield A Novel Regulatory T cell Cytokine
    LAUREN COLLISON; Fiscal Year: 2009
    Epstein barr virus induced gene 3 (EBI-3) is a soluble protein that shares structural similarities to the IL12 p40 chain...
  8. Probiotics-derived soluble proteins regulate intestinal inflammation
    Fang Yan; Fiscal Year: 2013
    ..We have successfully purified and cloned two novel LGG-derived soluble proteins (p40 and p75) that prevent cytokine-induced apoptosis through activating Akt in intestinal epithelial cells...
  9. Rac GTPase signaling during embryonic salivary gland branching morphogenesis
    Sharon Sequeira; Fiscal Year: 2012
    ..used in proposal: 2D, two-dimensional;3D, three-dimensional;BM, basement membrane;ECM, extracellular matrix;GEF, guanine nucleotide exchange factor;GTPase, guanosine triphosphate hydroxylase;IB, immunoblotting;IF, ..
  10. Effects of acute ethanol exposure on post burn intestinal immunity: role of IL-23
    Juan Luis Rendón; Fiscal Year: 2013
    ..our laboratory demonstrated decreased levels of Th17 effector cytokine IL-17 as well as decreased levels of the p40 subunit of IL-23 in Peyer's patches following alcohol intoxication and burn injury...
  11. Dissecting the role of one neuronal RhoGEF amongst many: the Kalirin-7 null mouse
    Richard E Mains; Fiscal Year: 2012
    ..Deficits in expression of Kalirin, a large, dual Rho GEF protein, are associated with increased iNOS levels in Alzheimer's disease brain and with decreased spine ..
  12. STRUCTURE AND FUNCTION OF PAXILLIN
    Christopher E Turner; Fiscal Year: 2012
    ..This will be combined with biochemical analysis of changes in intracellular signaling to include GEF activity assays, protein phosphorylation profiling and protein- protein interactions...
  13. Signaling Connections Controlling Cell Motility and Invasion
    David D Schlaepfer; Fiscal Year: 2013
    ..will focus on the molecular interactions of focal adhesion kinase (FAK) and a guanine nucleotide exchange factor (GEF) for Rho-family GTPases termed ARHGEF28 (alternative names are p190RhoGEF or Rgnef)...
  14. Protein Kinase C Signaling Mechanisms in Cancer
    Alan P Fields; Fiscal Year: 2013
    ..cell proliferation and invasion in vitro, and tumor formation in vivo;2) the guanine nucleotide exchange factor (GEF) Ect2 binds the PKC?/Par6 complex and activates Rac1, a key downstream effector of this complex;3) PKC? regulates ..
  15. 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...
  16. Multimeric Signaling Complexes in PRLr Transduction
    Charles V Clevenger; Fiscal Year: 2013
    ..binding of ligand, a complex of the Nek3 serine/threonine kinase and the Vav2 guanine nucleotide exchange factor (GEF) associates with the PRLr...
  17. Role of p190RhoGEF (Rgnef) in cell motility and tumor progression
    Nichol L G Miller; Fiscal Year: 2013
    ..Rgnef is a 190 kDa RhoA-specific GEF (also termed p190RhoGEF) involved in the regulation of integrin-initiated RhoA activation, focal adhesion (FA) ..
  18. Protective role of ANP in the models of acute lung injury
    Anna Birukova; Fiscal Year: 2013
    ..microtubule stabilization and regulation of microtubule-associated Rho-specific guanine nucleotide exchange factor GEF-H1...
  19. Role of Ypt/Rab GTPases in intra-cellular Trafficking
    Nava Segev; Fiscal Year: 2013
    ..Based on our results, we propose that activation of these Ypts is achieved by one modular GEF complex, TRAPP, which thereby coordinates steps of the exocytic pathway as well as its intersection with autophagy...
  20. ErbB receptor signaling via small G-proteins in breast cancer
    MARCELO GABRIEL KAZANIETZ; Fiscal Year: 2013
    ..revealed a prominent role for phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchanger-1 (P-Rex1), a Rac-GEF originally identified in neutrophils but not studied in any cancer so far...
  21. Regulation of androgen receptor activity in prostate cancer cells in an aged mous
    STEPHANIE OLGA PEACOCK; Fiscal Year: 2013
    ..activity requires the Vav3 pleckstrin homology (PH) domain, but not guanine nucleotide exchange factor (GEF) activity...
  22. Targeting the Fn14-Rac1 signaling pathway in invasive gliomas
    Nhan L Tran; Fiscal Year: 2012
    ..We found that Ect2, a guanine nucleotide exchange factor (GEF), is overexpressed in GBM, and that overexpression of both Ect2 and Fn14 is correlated directly with tumor grade ..
  23. BARRIER FUNCTION OF THE GI TRACT IN HEALTH AND DISEASE
    W Allan Walker; Fiscal Year: 2013
    ..Project 4 will determinethe role of GEF-H1, a guanine nucleotide exchange factor (GEF) for Rho, on epithelial cell responses to pathogens and examine the ..
  24. Molecular Mechanisms of RhoA-mediated Ca2+Sensitization in Vascular Smooth Muscle
    Avril V Somlyo; Fiscal Year: 2013
    ..data, which postulates that negative control is exerted on RhoA by cyclic nucleotides (cAMP) acting via the Rap1 GEF, Epac and Rap1 (another GTPase) to activate RhoA specific GAPs including ARAP3 and RA-RhoGAP...
  25. Inhibition of Stat3 and inflammatory cytokine production
    Lionel B Ivashkiv; Fiscal Year: 2013
    ..important for host defense against intracellular pathogens and Th1 responses: Il12a (encoding IL-12 p35), Il12b (p40) and Nos2 (iNOS). Expression of these genes is regulated by IRF1, IRF8 and the NF-?B family member c-Rel...
  26. Mechanism of G protein Activation by Ric-8A
    Stephen R Sprang; Fiscal Year: 2013
    ..Ric-8A is critical regulator of G? in this process. Ric-8A is a Guanine nucleotide Exchange Factor (GEF) that catalyzes the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) at the active site of ..
  27. Nuclear GTPase PIKE Regulation and Functions
    Keqiang Ye; Fiscal Year: 2013
    ..PLC-g1 activates PIKE by acting as a guanine nucleotide exchange factor (GEF)...
  28. STRUCTURAL ANALYSIS OF G PROTEIN REGULATORY MECHANISMS
    STEPHEN SPRANG; Fiscal Year: 2009
    ..The first aim of this proposal focuses on Ric-8A, a recently identified Guanine nucleotide Exchange Factor (GEF) for Gi-class G[unreadable] subunits (e.g...
  29. ELMO1, Dock180 and Glioma Invasion
    Shi Yuan Cheng; Fiscal Year: 2012
    ..binding partner, dedicator of cytokinesis 1 (Dock180) function as a bipartite guanine nucleotide exchange factor (GEF) that activates Rac1 and promotes cell migration of C. elegans, Drosophila and mammalian cells...
  30. Regulation of Arf GTPase activation at the trans-Golgi network
    J Christopher Fromme; Fiscal Year: 2013
    ..Arf GTPases are activated at the trans- Golgi network by the Arf-GEF (Guanine nucleotide Exchange Factor) proteins BIG1/ARFGEF1 and BIG2/ARFGEF2 in humans, and by the homologous Sec7p ..
  31. Elucidating a G-protein signaling pathway in E. histolytica amoebic colitis
    Dustin E Bosch; Fiscal Year: 2013
    ..EhG123) and a regulator of G protein signaling (RGS) domain-containing Rho guanine nucleotide exchange factor (GEF) from the E. histolytica genome...
  32. Regulation of Glioma Cell Migration by RasGRP3
    Chaya Brodie; Fiscal Year: 2010
    ..RasGRP3 is a guanine nucleotide exchange factor (GEF) that activates small GTPases including Ras and Rap1...
  33. Characterization of GEFT AS a Novel Glioblastoma Oncogene
    MILAN GIRISH CHHEDA; Fiscal Year: 2013
    ..targeting genes on regions commonly amplified in GBM and identified GEFT, a guanine nucleotide exchange factor (GEF), as essential for GBM cell proliferation and/or viability...
  34. Rap1 in VEGF signaling in endothelial cells
    Magdalena Chrzanowska-Wodnicka; Fiscal Year: 2013
    ..leading to elevated vascular permeability is in part relayed via interactions between activated Rap1, Rac1 and Rap1 GEF (Guanine nucleotide Exchange Factor) C3G...
  35. Novel therapeutic inhibition of the Rac oncogene in pancreatic cancer
    MARK A MC NIVEN; Fiscal Year: 2012
    ..Interestingly, a guanine nucleotide exchange factor (GEF) and activator of the Rac oncogene, termed Vav1, is a member of a broad class of Rac GEFs that has recently been ..
  36. GEF activity in circadian pacemaker neurons
    Justin Blau; Fiscal Year: 2012
    ..CG33275 is an unstudied gene which likely encodes a Guanine nucleotide Exchange Factor (GEF) that activates a Rho family GTPase...
  37. Defining the role and regulation of the RhoGEF Ect2 in ovarian cancer cells
    LAUREN PARKER HUFF; Fiscal Year: 2013
    ..Ect2 is a Dbl family guanine nucleotide exchange factor (GEF) that activates Rho family GTPases...
  38. Rho GTPase-mediated pathways in autoimmune arthritis
    Alessandra B Pernis; Fiscal Year: 2013
    ..interacting with IRF4, a transcription factor required for the differentiation of TH-17 cells, we cloned a novel GEF that we termed IBP (IRF-4 Binding Protein), also known as Def6...
  39. High throughput assay for novel pharmacological probes targeting cAMP signaling
    Xiaodong Cheng; Fiscal Year: 2012
    ..discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (Epac/cAMP-GEF)...
  40. Vav3 Oncogene Potentiation of Androgen Receptor Signaling in Prostate Cancer.
    Kerry L Burnstein; Fiscal Year: 2013
    ..We and others have demonstrated that Vav3, a Rho GTPase guanine nucleotide exchange factor (GEF), is upregulated during in vitro and in vivo progression of prostate cancer to androgen-independence in several ..
  41. ARF regulators in endocytic transport
    Victor W Hsu; Fiscal Year: 2013
    ..Second, we have identified Grp1 as the GEF that acts on ARF6 for the endocytic recycling of the glucose transporter type 4 (glut4), a process that is ..
  42. Roles of MyoGEF in cytokinesis
    Qize Wei; Fiscal Year: 2011
    ..Thus far, at least three GEFs, i.e. ECT2, GEF-H1, and MyoGEF, are implicated in regulating cytokinesis...
  43. REGULATION OF NEUTROPHIL RECEPTOR G PROTEIN INTERACTIONS
    Gary Bokoch; Fiscal Year: 2009
    ..We identified molecular targets for cytoskeletal regulation by PAK1, including GEF-H1, LIM kinase, and myosin light chain kinase...
  44. HORMONAL REGULATION OF MAP KINASE VIA RAP1 AND B-RAF
    Philip J S Stork; Fiscal Year: 2010
    ..that Rapt regulation of ERKs via cAMP is dictated by the choice of Rap1 guanine nucleotide exchange factor (GEF) utilized...
  45. Mapping the Architecture of Cancer Signaling Pathways
    Scott H Soderling; Fiscal Year: 2010
    ..It is well known that Rho GTPases are "signaling switches" that are turned "on" or "off" by GEF (Guanine nucleotide Exchange Factors) and GAP (GTPase Activating Proteins) proteins...
  46. IL-23 / Il-17 and Lung Host Defense
    Jay Kolls; Fiscal Year: 2009
    ..and the subsequent production of IL-23 (a novel heterodimeric cytokine composed of a unique p19 subunit and the p40 subunit of IL-12) by these cell populations which signal to T-cell to produce IL-17...
  47. Functional Role of Nck and Crk Binding Interactions
    Bruce J Mayer; Fiscal Year: 2012
    ..elucidate the molecular basis for the positive role for the Sos1 guanine nucleotide exchange factor (GEF) and the negative role for Abl tyrosine kinases in transformation by Crk;2...
  48. MECHANISMS & REGULATION OF PROTEIN SYNTHESIS
    ALBERT WAHBA; Fiscal Year: 1992
    The guanine nucleotide exchange factor (GEF) from rabbit reticulocytes which consists of five subunits will be further purified (Proc. Natl. Acad. Sci. U.S.A...
  49. Spatio-temporal dynamics of GEF-GTPase networks
    KLAUS MICHAEL HAHN; Fiscal Year: 2013
    ..PPG brings together team members with diverse expertise to develop innovative technologies enabling the study of GEF/GTPase networks in vivo, computational tools to extract network architecture and signaling kinetics from imaging ..
  50. Mechanisms of Innate Immune Regulation for Mucosal Homeostasis
    Hans Christian Reinecker; Fiscal Year: 2011
    ..We have identified the guanine nucleotide exchange factor H1 (GEF-H1) encoded by the arhgef2 gene as a required component of innate immune regulation by CARD-..
  51. SIGNALING VIA THE MULTIFUNCTIONAL TRIO PROTEIN
    Haruo Saito; Fiscal Year: 2001
    ..The multifunctional Trio protein contains a rac1-specific GEF domain, a rhoA-specific GEF domain, a protein serine\threonine kinase domain, and a number of auxiliary domains...
  52. RHOA EFFECTOR IN HIV-1 REPLICATION AND PATHOGENESIS
    Lishan Su; Fiscal Year: 2004
    ..gp41 (gp41C) interacts with and inhibits p115-RhoGEF, which is a specific guanine nucleotide exchange factor (GEF) and activator of RhoA...
  53. FUNCTION OF THE VAV PROTOONCOGENE
    Arthur Weiss; Fiscal Year: 2004
    ..The Vav family of proteins contains multiple modular domains including a guanine nucleotide exchange factor (GEF) domain that can regulate small GTPases of the Rho family...
  54. NOVEL SECOND MESSENGER SIGNALING IN THE STRIATUM
    ANN GRAYBIEL; Fiscal Year: 2003
    ..Many Ras GEFs, but until the work described, only Rap GEF, have been identified...
  55. The Pathway to Activation of the Vav Proto-Oncogene
    Michael Rosen; Fiscal Year: 2006
    ..Vav, a key regulator of lymphocyte signal transduction pathways, is a guanine nucleotide exchange factor (GEF) for Rho GTPases...
  56. Molecular immunologic role of cytokines in the development of malarial immunity
    JOHN MICHAEL ONGECHA; Fiscal Year: 2010
    ..IL-23 is a recently discovered pro-inflammatory cytokine that shares a common p40 subunit with IL-12...
  57. Role of PGE2 in CNS and peripheral autoimmune disorders
    Doina Ganea; Fiscal Year: 2010
    ..of the relevant signaling molecules and transcription factors involved in the PGE2 regulation of p19, p40, and p35 gene transcription...
  58. The Role of the Vasculature in the Pathogenesis of Arthritis
    DEAN YAW LI; Fiscal Year: 2013
    ..MYD88 binds to ARNO, an ARF-GEF that activates the small GTPase ARF6...
  59. Microbial Pattern Recognition and Signaling by the Adhesion GPCR BAI1
    James E Casanova; Fiscal Year: 2013
    ..to BAI1 triggers phagocytosis through a mechanism involving activation of the small GTPase Rac by the Elmo/Dock180 GEF complex, which interacts directly with BAI1...
  60. Targeting IL-12/23 p40 Pathways for the Control of GVHD
    Xue Zhong Yu; Fiscal Year: 2013
    ..Specifically, we hypothesize that targeting p40, IL-12R[unreadable]1 or their downstream signaling events will disrupt Th1/Th17 differentiation and thus control ..
  61. Novel Therapeutic Approach for Sepsis: Blocking the Vascular Response to Cytokine
    ALAN L MUELLER; Fiscal Year: 2012
    ..Dr. Li and colleagues further determined that ARF6 can be blocked through inhibition of its ARF-GEF, cytohesin2/ARNO, using a small molecule inhibitor, NAV838. Dr...
  62. Studies on the role of IL-23p19/IL-17 cascade in the pathogenesis of acute GVHD
    JOHN SECORD THOMPSON; Fiscal Year: 2012
    ..with bone marrow (BM) plus T- containing spleens (SCs) from mutant mice deficient in the p19 dimer of the IL-23 p19/p40 heterodimer develop aGVHD less frequently and less severely than BALB/c transplanted with normal wild type C57BL/6 ..
  63. A Bifunctional Katp Channel Activator and Redox Mimetic for BPD
    Kanneganti Murthy; Fiscal Year: 2013
    ..including eotaxin, G-CSF, GM-CSF, IFN-?, IL-1[unreadable], IL-2, IL4, IL-3, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17, IP-10, KC, LIF, LIX, MCP-1, M-CSF, MIG, MIP-1[unreadable], MIP-1[unreadable], ..
  64. PLD2, as a GEF or as a Lipase, is Central to Leukocyte Chemotaxis
    JULIAN G CAMBRONERO; Fiscal Year: 2013
    ..1) First, novel data in our lab has revealed an unexpected GEF activity that exists in the lipase PLD2...
  65. Yale Autoimmunity Center of Excellence
    Kevan C Herold; Fiscal Year: 2013
    ..The second trial is a Phase II trial of the anti-p40 mAb CNTO 1275 (Ustekinumab) for treatment of primary Sj"gren's syndrome...