gtpase activating proteins

Summary

Summary: Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.

Top Publications

  1. pmc A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex
    M J Matunis
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    J Cell Biol 135:1457-70. 1996
  2. ncbi A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2
    R Mahajan
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Cell 88:97-107. 1997
  3. ncbi Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles
    Elizabeth A Miller
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 114:497-509. 2003
  4. ncbi TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism
    Xiaojing Pan
    Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, UMass Medical School, Two Biotech, 373 Plantation Street, Worcester, Massachusetts 01605, USA
    Nature 442:303-6. 2006
  5. ncbi The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, 44139 Dortmund, Germany
    Science 277:333-8. 1997
  6. 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
  7. ncbi Current knowledge of the large RhoGAP family of proteins
    Joseph Tcherkezian
    Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada H3A 2B2
    Biol Cell 99:67-86. 2007
  8. ncbi Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking
    Mark Larance
    Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, Australia
    J Biol Chem 280:37803-13. 2005
  9. ncbi GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins
    E M Ross
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    Annu Rev Biochem 69:795-827. 2000
  10. 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

Research Grants

  1. Cellular Signaling in Alcoholism
    Subhash C Pandey; Fiscal Year: 2013
  2. STRUCTURE AND FUNCTION OF PAXILLIN
    Christopher E Turner; Fiscal Year: 2012
  3. Novel functions of RGS3
    Nickolai O Dulin; Fiscal Year: 2012
  4. Phosphoprotein CDP138 regulates glucose metabolism
    ZHEN YUE JIANG; Fiscal Year: 2013
  5. Role of Rab GAPs AS160 and Tbc1d1 in GLUT4 translocation and glucose homeostasis
    Susanna R Keller; Fiscal Year: 2013
  6. Chimaerins-receptors for diacylgly and phorbal esters
    MARCELO GABRIEL KAZANIETZ; Fiscal Year: 2012
  7. Mechanism and role of DLC-1 tumor suppressor loss in lung cancer
    Channing J Der; Fiscal Year: 2012
  8. Study of Anti-Survival signals in NF1
    CHANGYAN CHEN; Fiscal Year: 2013
  9. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID W CLAPP; Fiscal Year: 2012
  10. Myosin Functions in the Enterocyte
    Mark S Mooseker; Fiscal Year: 2012

Detail Information

Publications325 found, 100 shown here

  1. pmc A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex
    M J Matunis
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    J Cell Biol 135:1457-70. 1996
    ..Moreover, the variety and function of ubiquitin-like protein modifications in the cell may be more diverse than previously realized...
  2. ncbi A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2
    R Mahajan
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Cell 88:97-107. 1997
    ..Inhibition of nuclear protein import resulting from antibodies directed at NPC-associated RanGAP1 cannot be overcome by soluble cytosolic RanGAP1, indicating that GTP hydrolysis by Ran at RanBP2 is required for nuclear protein import...
  3. ncbi Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles
    Elizabeth A Miller
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Cell 114:497-509. 2003
    ..Together, our data support a model whereby Sec24p proteins contain multiple independent cargo binding domains that allow for recognition of a diverse set of sorting signals...
  4. ncbi TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism
    Xiaojing Pan
    Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, UMass Medical School, Two Biotech, 373 Plantation Street, Worcester, Massachusetts 01605, USA
    Nature 442:303-6. 2006
    ..Strong conservation of both catalytic fingers indicates that most TBC-domain GAPs may accelerate GTP hydrolysis by a similar dual-finger mechanism...
  5. ncbi The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, 44139 Dortmund, Germany
    Science 277:333-8. 1997
    ..Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state...
  6. 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
    ..Recent evidence suggests that these proteins may be potential therapeutic targets for developing drugs to treat various diseases, including cancer...
  7. ncbi Current knowledge of the large RhoGAP family of proteins
    Joseph Tcherkezian
    Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada H3A 2B2
    Biol Cell 99:67-86. 2007
    ..In the present Review, we discuss their regulation, biological functions and implication in human diseases...
  8. ncbi Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking
    Mark Larance
    Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, Australia
    J Biol Chem 280:37803-13. 2005
    ..These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4...
  9. ncbi GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins
    E M Ross
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    Annu Rev Biochem 69:795-827. 2000
    ..GAPs are regulated by various controls of their cellular concentrations, by complex interactions with G¿ or with G¿5 through an endogenous G-like domain, and by interaction with multiple other proteins...
  10. 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...
  11. ncbi Full intracellular retention of GLUT4 requires AS160 Rab GTPase activating protein
    Lorena Eguez
    Department of Biochemistry, Weill Cornell Medical School, New York, New York 10021, USA
    Cell Metab 2:263-72. 2005
    ..Our findings that AS160 knockdown only partially releases basal GLUT4 retention provides evidence that insulin signals to GLUT4 exocytosis by both AS160-dependent and -independent mechanisms...
  12. pmc ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif
    Joëlle Bigay
    CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, Sophia Antipolis, France
    EMBO J 24:2244-53. 2005
    ..This helix differs from classical amphipathic helices by the abundance of serine and threonine residues on its polar face...
  13. ncbi GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits
    D M Berman
    Department of Pharmacology University of Texas Southwestern Medical Center Dallas 75235, USA
    Cell 86:445-52. 1996
    ..RGS4 activates the GTPase activity of certain Gi alpha 1 mutants (e.g., R178C), but not others (e.g., Q204L). The GAP activity of RGS proteins is consistent with their proposed role as negative regulators of G protein-mediated signaling...
  14. pmc Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport
    F R Bischoff
    Division of Molecular Biology of Mitosis, German Cancer Research Center, Heidelberg
    Proc Natl Acad Sci U S A 92:1749-53. 1995
    ..Thus, a defect in either of the two antagonistic regulators of Ran would result in a shutdown of Ran-dependent transport processes, in agreement with the almost identical phenotypes described for such defects in budding yeast...
  15. ncbi Mutation of RGA1, which encodes a putative GTPase-activating protein for the polarity-establishment protein Cdc42p, activates the pheromone-response pathway in the yeast Saccharomyces cerevisiae
    B J Stevenson
    Department of Biology and Institute of Molecular Biology, University of Oregon, Eugene 97403, USA
    Genes Dev 9:2949-63. 1995
    ....
  16. ncbi BAR domains as sensors of membrane curvature: the amphiphysin BAR structure
    Brian J Peter
    Medical Research Council MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Science 303:495-9. 2004
    ..From this, we predict that BAR domains are in many protein families, including sorting nexins, centaurins, and oligophrenins. The universal and minimal BAR domain is a dimerization, membrane-binding, and curvature-sensing module...
  17. ncbi Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation
    Hiroyuki Sano
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 278:14599-602. 2003
    ..These findings strongly indicate that insulin-stimulated phosphorylation of AS160 is required for GLUT4 translocation and that this phosphorylation signals translocation through inactivation of the Rab GAP function...
  18. ncbi Requirement for a GTPase-activating protein in vesicle budding from the endoplasmic reticulum
    T Yoshihisa
    Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720
    Science 259:1466-8. 1993
    ..It appears that Sec23p represents a new class of GTPase-activating protein because its sequence shows no similarity to any known member of this family...
  19. ncbi Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators
    Shuai Chen
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 409:449-59. 2008
    ..These findings suggest that TBC1D1 and AS160 may have complementary roles in regulating vesicle trafficking in response to insulin and AMPK-activating stimuli in skeletal muscle...
  20. ncbi COPII-cargo interactions direct protein sorting into ER-derived transport vesicles
    M J Kuehn
    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley 94720, USA
    Nature 391:187-90. 1998
    ..Our results indicate that cargo packaging signals and soluble cargo adaptors are recognized by a recruitment complex comprising Sar1-GTP and Sec23/24...
  21. ncbi The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras
    Izumi Oinuma
    Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Science 305:862-5. 2004
    ..Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras...
  22. pmc ZDS1 and ZDS2, genes whose products may regulate Cdc42p in Saccharomyces cerevisiae
    E Bi
    Department of Biology, University of North Carolina, Chapel Hill 27599, USA
    Mol Cell Biol 16:5264-75. 1996
    ..As ZDS1 and ZDS2 have recently been identified also by numerous other groups studying a wide range of biological phenomena, the roles of Cdc42p in intracellular signaling may be more diverse than has previously been appreciated...
  23. pmc Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways
    Evelyn Fuchs
    Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany
    J Cell Biol 177:1133-43. 2007
    ..These results suggest that Shiga toxin trafficking to the Golgi is a multistep process controlled by several Rab GAPs and their target Rabs and that this process is discrete from ligand-induced EGF receptor trafficking...
  24. pmc The LD4 motif of paxillin regulates cell spreading and motility through an interaction with paxillin kinase linker (PKL)
    K A West
    Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, 750 East Adams St, Syracuse, NY 13210, USA
    J Cell Biol 154:161-76. 2001
    ..These data suggest that the paxillin association with PKL is essential for normal integrin-mediated cell spreading, and locomotion and that this interaction is necessary for the regulation of Rac activity during these events...
  25. pmc Role of DLC-1, a tumor suppressor protein with RhoGAP activity, in regulation of the cytoskeleton and cell motility
    T Y Kim
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Cancer Metastasis Rev 28:77-83. 2009
    ..We then delineate the characteristics of DLC-1 and other members of its family, and describe how they may have multiple effects on the regulation of cell polarity, actin organization, and cell migration...
  26. ncbi Arf GAPs: multifunctional proteins that regulate membrane traffic and actin remodelling
    Paul A Randazzo
    Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Building 37 Room 4118, Bethesda, MD 20892, USA
    Cell Signal 16:401-13. 2004
    ..The results discussed illustrate roles for both Arf-dependent and -independent activities in the regulation of cellular architecture...
  27. ncbi MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells
    A Toure
    Institut Cochin de Genetique Moleculaire, INSERM Unité 257, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
    J Biol Chem 273:6019-23. 1998
    ..Since rotundRacGAP deletion leads to male sterility in the fruit fly, the mgcRacGAP gene may prove likewise to play a key role in mammalian male fertility...
  28. pmc Relative contributions of Pseudomonas aeruginosa ExoU, ExoS, and ExoT to virulence in the lung
    Ciara M Shaver
    Department of Microbiology, Northwestern University Feinberg School of Medicine, 303 East Chicago Ave, Searle 6 495, Chicago, IL 60611, USA
    Infect Immun 72:6969-77. 2004
    ..The GAP activity of this protein had only a minor effect in vivo. The relative virulence associated with each of these type III effector proteins may have important prognostic implications for patients infected with P. aeruginosa...
  29. ncbi GAP control: regulating the regulators of small GTPases
    Andre Bernards
    MGH Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
    Trends Cell Biol 14:377-85. 2004
    ..So far, findings suggest that GAP activity is regulated by several mechanisms, including protein-protein interactions, phospholipid interactions, phosphorylation, subcellular translocation and proteolytic degradation...
  30. pmc RanBP2 associates with Ubc9p and a modified form of RanGAP1
    H Saitoh
    Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 5431, USA
    Proc Natl Acad Sci U S A 94:3736-41. 1997
    ..These results suggest Ubc9p's role in cell cycle regulation may involve either modification of nuclear transport substrates or the nuclear transport machinery...
  31. ncbi GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration
    Ri ichiroh Manabe
    Department of Cell Biology, University of Virginia, Charlottesville VA 22908, USA
    J Cell Sci 115:1497-510. 2002
    ..Thus, GIT1 is a component of a motile, multimolecular complex that traffics a set of signaling components to specific locations in the cell where they regulate localized activities...
  32. ncbi Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation
    Shuhei Ishikura
    Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada
    Am J Physiol Cell Physiol 295:C1016-25. 2008
    ..These results support a model whereby AS160, Rab8A, and myosin Vb are required for insulin-induced GLUT4 translocation in muscle cells, potentially as part of a linear signaling cascade...
  33. ncbi Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity
    Takashi Itoh
    Fukuda Initiative Research Unit, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Genes Cells 11:1023-37. 2006
    ....
  34. pmc An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase
    J D Hildebrand
    Department of Microbiology, Health Sciences Center, University of Virginia, Charlottesville 22908, USA
    Mol Cell Biol 16:3169-78. 1996
    ..We suggest that Graf may function to mediate cross talk between the tyrosine kinases such as FAK and the Rho family GTPase that control steps in integrin-initiated signaling events...
  35. ncbi Dissection of COPII subunit-cargo assembly and disassembly kinetics during Sar1p-GTP hydrolysis
    Ken Sato
    Molecular Membrane Biology Laboratory, RIKEN Discovery Research Institute, PRESTO, Japan Science and Technology Agency, Hirosawa, Wako, Saitama
    Nat Struct Mol Biol 12:167-74. 2005
    ..These data suggest a model for the maintenance of kinetically stable prebudding complexes during the Sar1p GTPase cycle that regulates cargo sorting into transport vesicles...
  36. pmc Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p
    Amy S Gladfelter
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    J Cell Biol 156:315-26. 2002
    ....
  37. ncbi Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting
    Jaewon Ko
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305 701, Korea
    J Neurosci 23:1667-77. 2003
    ..These results suggest that the GIT1-liprin-alpha interaction is required for AMPA receptor targeting and that GIT1 may play an important role in the organization of presynaptic and postsynaptic multiprotein complexes...
  38. ncbi The small G proteins of the Arf family and their regulators
    Alison K Gillingham
    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Annu Rev Cell Dev Biol 23:579-611. 2007
    ..Here we review what is known about all the members of the Arf family, along with the known regulatory molecules that convert them between GDP- and GTP-bound states...
  39. ncbi The CDM protein DOCK2 in lymphocyte migration
    Karin Reif
    Howard Hughes Medical Institute, Dept of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143 0414, USA
    Trends Cell Biol 12:368-73. 2002
    ..Here, we review the role of DOCK2 in lymphocyte homing to lymphoid tissues and discuss recent findings for other CDM family molecules that provide a basis for understanding how DOCK2 might function in lymphocytes...
  40. 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...
  41. pmc SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex
    M J Matunis
    Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York 10021, USA
    J Cell Biol 140:499-509. 1998
    ..This nuclear localization signal, and the presence of nine leucine-rich nuclear export signal motifs, suggests that RanGAP1 may shuttle between the nucleus and the cytoplasm...
  42. ncbi The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic
    Farah S L Thong
    Programme in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
    Diabetes 56:414-23. 2007
    ..Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake...
  43. 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...
  44. ncbi Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP
    K Rittinger
    National Institute for Medical Research, London, UK
    Nature 388:693-7. 1997
    ....
  45. pmc ADP-ribosylation factor 6 and a functional PIX/p95-APP1 complex are required for Rac1B-mediated neurite outgrowth
    Chiara Albertinazzi
    Cell Adhesion Unit, Department of Molecular Biology and Functional Genomics, S Raffaele Scientific Institute, 20132 Milan, Italy
    Mol Biol Cell 14:1295-307. 2003
    ..Our data support a role of p95-APP1 as a specific regulator of Arf6 in the control of membrane trafficking during neuritogenesis...
  46. ncbi A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains
    P Chardin
    Institut de Pharmacologie Moleculaire et Cellulaire du CNRS, Valbonne, France
    Nature 384:481-4. 1996
    ..We propose that other proteins with a Sec7 domain regulate different members of the ARF family...
  47. ncbi Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1
    S Kuroda
    Division of Signal Transduction, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma 630 01, Japan
    J Biol Chem 271:23363-7. 1996
    ..Moreover, IQGAP was accumulated at the cell-cell junction in MDCK cells, where alpha-catenin and ZO-1 were localized. These results suggest that IQGAP is a novel target molecule for Cdc42 and Rac1...
  48. ncbi Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 regulator of kinase (Crk) proteins
    Jianjun Sun
    Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    J Biol Chem 278:32794-800. 2003
    ..ExoS did not ADP-ribosylate Crk-I. ADP-ribosylation of Crk-I may be responsible for the anti-phagocytosis phenotype elicited by ExoT in mammalian cells...
  49. ncbi AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle
    Henning F Kramer
    Joslin Diabetes Center Research Division, Metabolism Section, Massachusetts 02215, USA
    J Biol Chem 281:31478-85. 2006
    ..Our findings directly implicate AS160 as a critical convergence factor for independent stimulators of skeletal muscle glucose uptake...
  50. ncbi Molecular dissection of the semaphorin 4D receptor plexin-B1-stimulated R-Ras GTPase-activating protein activity and neurite remodeling in hippocampal neurons
    Izumi Oinuma
    Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606 8502, Japan
    J Neurosci 24:11473-80. 2004
    ..These results indicate that Rnd1 opens the two R-Ras GAP domains of Plexin-B1, and Sema4D-induced receptor clustering stimulates R-Ras GAP activity and neurite remodeling in hippocampal neurons...
  51. ncbi A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II
    H J Chen
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Neuron 20:895-904. 1998
    ..Inhibition of p135 SynGAP by CaMKII will stop inactivation of GTP-bound Ras and thus could result in activation of the mitogen-activated protein (MAP) kinase pathway in hippocampal neurons upon activation of NMDA receptors...
  52. pmc Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules
    Takeshi Nakamura
    Department of Molecular Genetics, National Institute for Longevity Sciences, Program of Protecting the Brain, CREST, JST, Oobu, Aichi 474 8522, Japan
    Mol Cell Biol 22:8721-34. 2002
    ..These results suggest that Grit, a novel TrkA-interacting protein, regulates neurite outgrowth by modulating the Rho family of small GTPases...
  53. ncbi An Eps homology (EH) domain protein that binds to the Ral-GTPase target, RalBP1
    A Yamaguchi
    Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 272:31230-4. 1997
    ..Thus, Reps1 may coordinate the cellular actions of activated EGF receptors and Ral-GTPases...
  54. ncbi Rich, a rho GTPase-activating protein domain-containing protein involved in signaling by Cdc42 and Rac1
    N Richnau
    Ludwig Institute for Cancer Research, Biomedical Center, Box 595, S 751 24 Uppsala, Sweden
    J Biol Chem 276:35060-70. 2001
    ....
  55. pmc The fibronectin-binding integrins alpha5beta1 and alphavbeta3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis
    Erik H J Danen
    Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands
    J Cell Biol 159:1071-86. 2002
    ..Our findings demonstrate that the pattern of fibronectin receptors expressed on a cell dictates the ability of fibronectin to stimulate RhoA-mediated organization of cell matrix adhesions...
  56. pmc Disappearance of the budding yeast Bub2-Bfa1 complex from the mother-bound spindle pole contributes to mitotic exit
    Roberta Fraschini
    Dipartimento di Biotecnologie e Bioscienze, Universita di Milano Bicocca, 20126 Milano, Italy
    J Cell Biol 172:335-46. 2006
    ..Moreover, it correlates with the passage of one spindle pole through the bud neck because it needs septin ring formation and bud neck kinases...
  57. ncbi Suppression of Drosophila cellular immunity by directed expression of the ExoS toxin GAP domain of Pseudomonas aeruginosa
    Amelie Avet-Rochex
    CEA Grenoble, Departement de Reponse et Dynamique Cellulaires, UMR5092 CEA CNRS UJF, 17, Rue des Martyrs 38054 Grenoble Cedex 9, France
    Cell Microbiol 7:799-810. 2005
    ..Our results highlight the major contribution of cellular immunity during the first hours after Drosophila infection by P. aeruginosa, an opportunist pathogen affecting patients with pathologies associated to a reduced leukocyte number...
  58. pmc Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle
    Eric B Taylor
    The Joslin Diabetes Center Section on Metabolism and Proteomics Core and Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    J Biol Chem 283:9787-96. 2008
    ..TBC1D1 is a major PAS immunoreactive protein in skeletal muscle that is phosphorylated in vivo by insulin, AICAR, and contraction. Both Akt and AMPK phosphorylate TBC1D1, but AMPK may be the more robust regulator...
  59. ncbi Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer curvature
    Joëlle Bigay
    Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, 660 route des Lucioles, 06560 Valbonne Sophia Antipolis, France
    Nature 426:563-6. 2003
    ..This leads to a model for COPI dynamics in which GTP hydrolysis in Arf1 is organized temporally and spatially according to the changes in lipid packing induced by the coat...
  60. ncbi A murine homolog of the yeast RNA1 gene is required for postimplantation development
    J DeGregori
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2363
    Genes Dev 8:265-76. 1994
    ..These similarities suggest that Fug1 may be required for developmental changes in RNA processing or chromatin structure prior to gastrulation...
  61. ncbi The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors
    Richard T Premont
    Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Cell Signal 16:1001-11. 2004
    ..Thus, GIT and PIX proteins are tightly associated as a multimeric nexus capable of linking together important signaling molecules, including PAKs...
  62. pmc ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells
    Wei Liu
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 168:1053-63. 2005
    ..These data suggest that ArfGAP1, coatomer and Arf1 play interdependent roles in the assembly-disassembly cycle of the COPI coat in vivo...
  63. ncbi Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP
    D T Pak
    Department of Neurobiology, Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Neuron 31:289-303. 2001
    ..The effects of SPAR on spine morphology depend on the RapGAP and actin-interacting domains, implicating Rap signaling in the regulation of postsynaptic structure...
  64. pmc The roles of bud-site-selection proteins during haploid invasive growth in yeast
    Paul J Cullen
    Institute of Molecular Biology, University of Oregon, Eugene 97403 1229, USA
    Mol Biol Cell 13:2990-3004. 2002
    ..In the bud8 mutant in glucose-limiting conditions, apical growth and bud site selection were uncoupled processes. Finally, we report that diploid cells starved for glucose also initiate the filamentous growth response...
  65. pmc Identification of a GTPase-activating protein homolog in Schizosaccharomyces pombe
    Y Imai
    Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Japan
    Mol Cell Biol 11:3088-94. 1991
    ....
  66. ncbi Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family
    P J Cullen
    Inositide Laboratory, Babraham Institute, Cambridge, UK
    Nature 376:527-30. 1995
    ..In vitro it shows GAP activity against both Rap and Ras, but only the Ras GAP activity is inhibited by phospholipids and is specifically stimulated by Ins(1,3,4,5)P4...
  67. ncbi Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity
    Masanori Mishima
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030, Vienna, Austria
    Dev Cell 2:41-54. 2002
    ..Biochemical studies indicate that this complex, named centralspindlin, is a heterotetramer. Centralspindlin, but not its individual components, strongly promotes microtubule bundling in vitro...
  68. ncbi Genetic alteration and expression of the phosphoinositol-3-kinase/Akt pathway genes PIK3CA and PIKE in human glioblastomas
    C B Knobbe
    Department of Neuropathology, Heinrich Heine University, Dusseldorf, Germany
    Neuropathol Appl Neurobiol 31:486-90. 2005
    ..Taken together, our data support an important role of PIK3CA and PIKE gene aberrations in the molecular pathogenesis of primary glioblastomas...
  69. ncbi Regulation of ARNO nucleotide exchange by a PH domain electrostatic switch
    L C Santy
    Combined Program in Pediatric Gastroenterology and Nutrition Massachusetts General Hospital East, Charlestown, Massachusetts 02129, USA
    Curr Biol 9:1173-6. 1999
    ..This mechanism allows regulation of ARNO lipid binding and exchange activity at two levels, phosphoinositide-dependent recruitment and PKC-dependent displacement from the membrane...
  70. ncbi GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor
    Judith Haendeler
    Center for Cardiovascular Research and Department of Medicine, University of Rochester, Rochester, New York 14642, USA
    J Biol Chem 278:49936-44. 2003
    ..We propose that GIT1 is a novel regulator of PLCgamma function that mediates PLCgamma activation by c-Src and integrates signal transduction by GPCRs and TKRs...
  71. ncbi Pseudomonas aeruginosa ExoS and ExoT
    J T Barbieri
    Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plk Road, Milwaukee, WI 53226, USA
    Rev Physiol Biochem Pharmacol 152:79-92. 2004
    ..Protein modeling predicts that electrostatic interactions contribute to the substrate specificity of the ADP-ribosyltransferase domains of ExoS and ExoT...
  72. ncbi Mice with a homozygous gene trap vector insertion in mgcRacGAP die during pre-implantation development
    T Van de Putte
    Department of Cell Growth, Differentiation and Development VIB 07, Flanders Interuniversity Institute for Biotechnology VIB and Laboratory of Molecular Biology Celgen, University of Leuven, Herestraat 49, 3000, Leuven, Belgium
    Mech Dev 102:33-44. 2001
    ..In addition, the severe phenotype of null embryos indicates that mgcRacGAP is functionally non-redundant and cannot be substituted by other GAPs during early cleavage of the mammalian embryo...
  73. ncbi MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody
    K Hirose
    Division of Hematopoietic Factors, The Institute of Medical Science, University of Tokyo, Minato ku Tokyo 108 8639, Japan
    J Biol Chem 276:5821-8. 2001
    ..Furthermore, using a GAP-inactive mutant, we have shown that the GAP activity of MgcRacGAP is required for cytokinesis, suggesting that inactivation of the Rho family of GTPases may be required for normal progression of cytokinesis...
  74. ncbi Use of MLL/GRAF fusion mRNA for measurement of minimal residual disease during chemotherapy in an infant with acute monoblastic leukemia (AML-M5)
    Monika Wilda
    Genes Chromosomes Cancer 43:424-6. 2005
  75. ncbi Control of the yeast bud-site assembly GTPase Cdc42. Catalysis of guanine nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3
    Y Zheng
    Department of Pharmacology, Cornell University, Ithaca, New York 14850
    J Biol Chem 269:2369-72. 1994
    ..These studies demonstrate that Cdc24 and Bem3 have GDP-release factor activity and GTPase-activating protein activity, respectively, toward the essential bud-site assembly GTPase Cdc42...
  76. pmc Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160
    Anja Zeigerer
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Mol Biol Cell 15:4406-15. 2004
    ..These data support a model in which insulin signaling to the exocytosis machinery (AS160 dependent) is distinct from its signaling to the internalization machinery (AS160 independent)...
  77. ncbi Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins
    Yong Zhang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9040, USA
    Nat Cell Biol 5:578-81. 2003
    ..Point mutations in the GAP domain of Tsc2 disrupted its ability to regulate Rheb without affecting the ability of Tsc2 to form a complex with Tsc1. Our studies identify Rheb as a molecular target of the TSC tumour suppressors...
  78. ncbi A GTPase-activating protein binds STAT3 and is required for IL-6-induced STAT3 activation and for differentiation of a leukemic cell line
    Yukio Tonozuka
    Division of Cellular Therapy, Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Blood 104:3550-7. 2004
    ..All together, our data not only reveal an important role for MgcRacGAP in STAT3 activation, but also demonstrate that MgcRacGAP regulates IL-6-induced cellular differentiation in which STAT3 plays a pivotal role...
  79. pmc c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 283:24295-9. 2008
    ..Therefore, c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1 ubiquitination and NF-kappaB activation...
  80. pmc Function and regulation of Tumbleweed (RacGAP50C) in neuroblast proliferation and neuronal morphogenesis
    Ann Y N Goldstein
    Department of Biological Sciences and Neurosciences Program, Stanford University, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 102:3834-9. 2005
    ..Taken together with previous studies of RacGAP50C in regulating cytokinesis, we propose that Tum serves as a scaffolding protein in regulating cell division but acts as a GAP to limit axon growth in postmitotic neurons...
  81. ncbi The nucleoporin RanBP2 has SUMO1 E3 ligase activity
    Andrea Pichler
    Max Planck Institute for Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Cell 108:109-20. 2002
    ..Our findings place SUMOylation at the cytoplasmic filaments of the NPC and suggest that, at least for some substrates, modification and nuclear import are linked events...
  82. ncbi Identification of a Sec4p GTPase-activating protein (GAP) as a novel member of a Rab GAP family
    L L Du
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 273:3253-6. 1998
    ..The finding that yeast Rab GAPs share homology with proteins in other species, such as Caenorhabditis elegans and human, suggests the existence of a conserved Rab GAP family...
  83. pmc Activation of ARF6 by ARNO stimulates epithelial cell migration through downstream activation of both Rac1 and phospholipase D
    L C Santy
    Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
    J Cell Biol 154:599-610. 2001
    ....
  84. ncbi FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling
    Yasutaka Ohta
    Hematology Division, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Nat Cell Biol 8:803-14. 2006
    ..FilGAP is, therefore, a mediator of the well-established antagonism of Rac by RhoA that suppresses leading edge protrusion and promotes cell retraction to achieve cellular polarity...
  85. ncbi Identification of adherens junction-associated GTPase activating proteins by the fluorescence localization-based expression cloning
    Miho Matsuda
    Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Exp Cell Res 314:939-49. 2008
    ..Furthermore, cDNAs for ARHGAP12 and SPAL3, two putative GTPase activating proteins (GAPs) for small G proteins, were cloned as novel components of the junctional complex...
  86. pmc Regulation of cytokinesis by Rho GTPase flux
    Ann L Miller
    Department of Zoology, University of Wisconsin Madison, Madison, WI 53706, USA
    Nat Cell Biol 11:71-7. 2009
    ..by guanine nucleotide exchange factors (GEFs) initiates a particular event, and Rho inactivation by GTPase activating proteins (GAPs) terminates that event...
  87. pmc Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes
    D Cox
    Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA
    J Exp Med 186:1487-94. 1997
    ....
  88. ncbi RGSZ1, a Gz-selective RGS protein in brain. Structure, membrane association, regulation by Galphaz phosphorylation, and relationship to a Gz gtpase-activating protein subfamily
    J Wang
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 273:26014-25. 1998
    ..Phosphorylation of Galphaz by protein kinase C inhibited the GAP activity of RGSZ1 and other RGS proteins, providing a mechanism for potentiation of Gz signaling by protein kinase C...
  89. ncbi Transport of glutathione conjugates and chemotherapeutic drugs by RLIP76 (RALBP1): a novel link between G-protein and tyrosine kinase signaling and drug resistance
    Sanjay Awasthi
    Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX 76019, USA
    Int J Cancer 106:635-46. 2003
    ....
  90. pmc Role of p120 Ras-GAP in directed cell movement
    S V Kulkarni
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5
    J Cell Biol 149:457-70. 2000
    ..This observation suggests a specific function for Ras-GAP separate from Ras regulation in cell motility...
  91. ncbi Intra-endosomal pH-sensitive recruitment of the Arf-nucleotide exchange factor ARNO and Arf6 from cytoplasm to proximal tubule endosomes
    B Maranda
    Program in Membrane Biology and Renal Unit, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, 02129 2020, USA
    J Biol Chem 276:18540-50. 2001
    ..This mechanism may play an important role in the pH-dependent regulation of receptor-mediated endocytosis in proximal tubules in situ...
  92. pmc Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase
    Otilia V Vieira
    Cell Biology Program, Hospital for Sick Children and Department of Biochemistry, University of Toronto, Ontario M5G 1X8, Canada
    Mol Cell Biol 23:2501-14. 2003
    ..We propose that Rab5 activates both PI3K-dependent and PI3K-independent effectors that act in parallel to promote phagosome maturation...
  93. pmc Yeast rab GTPase-activating protein Gyp1p localizes to the Golgi apparatus and is a negative regulator of Ypt1p
    L L Du
    Department of Molecular Biophysics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Mol Biol Cell 12:1215-26. 2001
    ..These results establish that Gyp1p functions on the Golgi as a negative regulator of Ypt1p...
  94. pmc Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study
    Apiradee Sriwijitkamol
    Texas Diabetes Institute, and Diabetes Division, University of Texas Health Science Center at San Antonio, TX 78207, USA
    Diabetes 56:836-48. 2007
    ..Our findings suggest that obese type 2 diabetic subjects may need to exercise at higher intensity to stimulate the AMPK-AS160 axis to the same level as lean subjects...
  95. 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...
  96. ncbi GTPase activating proteins: structural and functional insights 18 years after discovery
    K Scheffzek
    Structural and Computational Biology Programme and Developmental Biology Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Cell Mol Life Sci 62:3014-38. 2005
    ..While the rate of GNBP-mediated GTP hydrolysis is intrinsically slow, direct interaction with GTPase activating proteins (GAPs) accelerates the reaction by up to five orders of magnitude in vitro...
  97. pmc Sec24p and Iss1p function interchangeably in transport vesicle formation from the endoplasmic reticulum in Saccharomyces cerevisiae
    T Kurihara
    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California 94720, USA
    Mol Biol Cell 11:983-98. 2000
    ..Abundant proteins in the purified vesicles produced with Sec23p/Iss1p were indistinguishable from those in the regular COPII vesicles produced with Sec23p/Sec24p...
  98. ncbi Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation
    P Billuart
    INSERM U129 ICGM, Faculté de Médecine Cochin, Paris, France
    Nature 392:923-6. 1998
    ..Such activation is known to affect cell migration and outgrowth of axons and dendrites in vivo. Our results demonstrate an association between cognitive impairment and a defect in a signalling pathway that depends on a Ras-like GTPase...
  99. ncbi Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP
    N Nassar
    Department of Pharmacology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA
    Nat Struct Biol 5:1047-52. 1998
    ..Comparison of the structures for the wild type and mutant Cdc42GAP complexes provides important insights into the GAP-catalyzed GTP hydrolytic reaction...
  100. ncbi ACAP1 promotes endocytic recycling by recognizing recycling sorting signals
    Jun Dai
    Division of Rheumatology, Immunology, and Allergy, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 7:771-6. 2004
    ..Taken together, these findings indicate that ACAP1 promotes cargo sorting by recognizing recycling sorting signals...
  101. ncbi The GGAs promote ARF-dependent recruitment of clathrin to the TGN
    R Puertollano
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
    Cell 105:93-102. 2001
    ..These observations suggest that the GGAs could function to link clathrin to membrane-bound ARF.GTP...

Research Grants70

  1. Cellular Signaling in Alcoholism
    Subhash C Pandey; Fiscal Year: 2013
    ....
  2. STRUCTURE AND FUNCTION OF PAXILLIN
    Christopher E Turner; Fiscal Year: 2012
    ..controlling the activity of their key regulators, the guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) remain poorly understood...
  3. Novel functions of RGS3
    Nickolai O Dulin; Fiscal Year: 2012
    ..Therefore, defining the molecular mechanisms of T cell activation and differentiation may lead to a better understanding the pathogenesis of these diseases. ..
  4. Phosphoprotein CDP138 regulates glucose metabolism
    ZHEN YUE JIANG; Fiscal Year: 2013
    ..Third, we observed that CDP138 interacts with TBC1D4/TBC1D1 and RalBP1, GTPase activating proteins for Rab10/Rab8A/Rab13 and Rac1, respectively...
  5. Role of Rab GAPs AS160 and Tbc1d1 in GLUT4 translocation and glucose homeostasis
    Susanna R Keller; Fiscal Year: 2013
    ..Studies in cultured fat and muscle cells attribute a role in GLUT4 retention and release to the two Rab GTPase activating proteins (Rab GAPs), AS160 and Tbc1d1...
  6. Chimaerins-receptors for diacylgly and phorbal esters
    MARCELO GABRIEL KAZANIETZ; Fiscal Year: 2012
    ..This proposal will investigate the relevance of 2-chimaerin in breast cancer progression as well as key regulatory mechanisms that control its activation and function. ..
  7. Mechanism and role of DLC-1 tumor suppressor loss in lung cancer
    Channing J Der; Fiscal Year: 2012
    ..Hence, we believe that our elucidation of the mechanism by which DLC-1 loss may deregulate Rho GTPases and promote NSCLC growth may define novel directions for targeted therapies for lung cancer treatment. ..
  8. Study of Anti-Survival signals in NF1
    CHANGYAN CHEN; Fiscal Year: 2013
    ....
  9. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID W CLAPP; Fiscal Year: 2012
    ..If the hypothesis is correct, we would predict that developing small molecules that inhibit Pak1 function could be useful as a molecular therapy for treatment of plexiform neurofibromas. ..
  10. Myosin Functions in the Enterocyte
    Mark S Mooseker; Fiscal Year: 2012
    ..g. cystic fibrosis transmembrane conductance regulator, Na+/phosphate exchanger 2b,Toll-like receptor 4) will be explored. ..
  11. Regulation of Cytokinesis and Tumor Formation by RhoA
    ANN LOUISE MILLER; Fiscal Year: 2013
    ..Finally, I will test whether cytokinesis failure induced by other Rho zone regulators, especially those that are up- or down-regulated or mutated in human tumors, promotes tumor formation. ..
  12. Regultion of p53 Deubiquitination
    Zhenkun Lou; Fiscal Year: 2013
    ..We will investigate the regulation of p53 by a novel p53 deubiquitinase USP10, which will provide important insights into the molecular mechanism of p53 regulation and tumor suppression. ..
  13. The Roles of Tumor Microenvironment in Neurofibroma Development and Therapeutics
    Lu Le; Fiscal Year: 2013
    ..An increased understanding of the role of non-neoplastic tumor-associated cells may lead to new directions for cancer therapy and prevention. ..
  14. Role of Ubiquitin in Cardiovascular System
    Song Li; Fiscal Year: 2013
    ..1 ..
  15. Regulation of the mTOR Pathway By Nutrients
    David M Sabatini; Fiscal Year: 2013
    ..Furthermore, some of the signaling mechanisms we uncover may serve in the future as targets for drug development. ..
  16. Defining the Mammalian Intercellular Bridge Interactome
    Martin M Matzuk; Fiscal Year: 2010
    ..Our proposed Specific Aims will also help us to develop additional high throughput screening assays for the identification of small molecule disruptors of the intercellular bridge. ..
  17. Molecular Analysis and Role of RGS6 as a Novel Growth Suppressor
    Rory A Fisher; Fiscal Year: 2010
    ..This work will determine how RGS6 works and will determine the basis for loss of RGS6 expression in human cancers. These studies could contribute to novel approaches in cancer therapy. ..
  18. Molecular Mechanisms of RhoA-mediated Ca2+Sensitization in Vascular Smooth Muscle
    Avril V Somlyo; Fiscal Year: 2013
    ..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 by catalyzing the hydrolysis of GTP to GDP (..
  19. The TSC-mTOR pathway in cellular and organismal energy metabolism
    Kun Liang Guan; Fiscal Year: 2013
    ..This proposal will investigate the function of TSC-mTOR in affecting leptin signaling and appetite control. The information generated from this project will provide new insights into to appetite regulation, obesity, and diabetes. ..
  20. Signal transduction in C. neoformans
    Jennifer K Lodge; Fiscal Year: 2012
    ..regulators of the pathway, specifically the Rho proteins and the guanine exchange factors and the GTPase activating proteins. Our preliminary data indicates that this part of the pathway is distinct from S. cerevisiae...
  21. 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. ..
  22. analysis of srGAP2 in cortical development in vitro and in vivo
    Jaeda Coutinho-Budd; Fiscal Year: 2012
    ..Enhancing our understanding of the mechanisms underlying srGAP2 function in neurite formation and neuronal migration will improve our understanding of the molecular mechanisms underlying cortical development. ..
  23. Brain Endothelial Cell Receptor for Escherichia coli
    Brian M Stoltz; Fiscal Year: 2013
    ..coli induced meningitis in newborn rats. Translational medicine is the outcome of this application in which studies of basic biology and applied technology to develop new strategies of prevention will be integrated. ..
  24. Preclinical Testing of Targeted Therapies for Neurofibromas
    DAVID W CLAPP; Fiscal Year: 2011
    ..Finally, using a combination of PET and CT imaging, we now have the ability to image the development, growth, and metabolism of plexiform neurofibromas in genetically engineered mice in vivo as a function of time. ..
  25. Genetic modulation of Wingless/Wnt signaling
    AMY M BEJSOVEC; Fiscal Year: 2012
    ..Experiments proposed here will use both the fruitfly model system and cultured human cells to study newly-discovered genetic factors that regulate Wnt signaling. ..
  26. Mother Centriole Appendages Regulate the AMIS Compartment and Cilogenesis.
    Heidi Hehnly; Fiscal Year: 2013
    ..Most importantly, this proposal may provide insights describing how disruption of the proposed molecular interactions may lead to disease phenotypes in ciliopathy patients. ..
  27. NMR Approaches to Membrane Associated ARF Complexes
    James H Prestegard; Fiscal Year: 2013
    ..abstract_text> ..
  28. Modeling Multi-step Leukemogenesis Nf1 and Kras Mutant Mice
    JENNIFER LAUCHLE; Fiscal Year: 2009
    ..The goal of this project is to model the multi-step process by which a normal cell transforms into leukemia. Improved understanding of these cellular changes will inform drug design and improve treatment and outcome for AML. ..
  29. High Throughput Assay Development for ARFGAP Modulators
    Qisheng Zhang; Fiscal Year: 2011
    ....
  30. Mechanism of cell polarization and asymmetric segregation of ageing determinants
    Rong Li; Fiscal Year: 2013
    ..one of the evolutionarily conserved, master regulators of cell polarity, and delayed activation of Cdc42 GTPase activating proteins (GAPs) are crucial mechanisms of the actin-independent symmetry breaking...
  31. PTSD-like phenotype of mice lacking GIT2
    Richard T Premont; Fiscal Year: 2011
    ..A deeper understanding of how GIT2 functions to regulate anxiety and the extinction of fear may provide insights into human fear and anxiety disorders such as PTSD. ..
  32. Cytoskeletal Oscillations: Mathematical Modeling Integrated with Experiments
    Kenneth A Jacobson; Fiscal Year: 2013
    ..A slow negative feedback loop involving GTPase activating proteins (GAPs), which deactivate RhoA, ensures RhoA activity remains localized as the wave travels...
  33. (PQD1) Response and Resistance to Inhibitors of Ras Effectors in Blood Cancers
    Kevin M Shannon; Fiscal Year: 2013
    ....
  34. p21-Activated Kinases as New Therapeutic Targets in Neurofibromatosis Type 1
    JONATHAN D CHERNOFF; Fiscal Year: 2013
    ..abstract_text> ..
  35. Yersinia Type III Transport of Yop Proteins into Immune Cells
    Olaf Schneewind; Fiscal Year: 2013
    ..Such knowledge can then be exploited to search for small molecule inhibitors that block the pathogenesis of microbes that rely on type III secretion systems to establish human infectious diseases. ..
  36. RASA1-mediated control of lymphatic vessel growth and function
    Philip D King; Fiscal Year: 2012
    ..Studies are also of direct relevance to our understanding of the etiology of a vascular disease in humans known as CM- AVM. ..
  37. The regulation and cellular activities of the Arl2 GTPase
    Richard A Kahn; Fiscal Year: 2013
    ....
  38. GAPs in Signaling to the Spine and Retardation: Mechanisms and the Role of WRP
    Scott H Soderling; Fiscal Year: 2012
    ..It is also expected that knowledge gained in these studies will shed light on other forms of neuropathologies that involve abnormal Rho-GTPase signaling and mechanisms that normally regulate neuronal connectivity. ..
  39. Drosophila models of human cognitive disorders: NF1 and Noonan syndrome
    Yi Zhong; Fiscal Year: 2012
    ..Study of these mutations will allow us gaining insights into molecular basis underlying memory retrieval and memory formation. Such understanding will in turn facilitate development of treatment for the disorders. ..
  40. Modulation of G proteins by Growth Factors
    Pradipta Ghosh; Fiscal Year: 2013
    ..Spectrometry, biophysical analysis of phosphoprotein, protein-protein interaction assays with GEFs, GTPase activating proteins (GAPs), guanidine dissociation inhibitors (GDIs) and GPCRs, computational modeling, and scratch-wound ..
  41. REGULATION OF PROTEIN TRAFFICKING IN ADIPOCYTES
    Mike M Mueckler; Fiscal Year: 2013
    ..It is directly relevant to understanding the molecular mechanisms involved in the regulation of whole body glucose homeostasis and its derangement in insulin resistant states such as diabetes, obesity, and metabolic syndrome. ..
  42. A RasGAP-microRNA connection in cardiac hypertrophy
    Maha Abdellatif; Fiscal Year: 2012
    ..post-transcriptional regulation of miR-1. Aim 2) to study the role of RasGAP and miR-1 during cardiac hypertrophy in a mouse model. ..
  43. The Function of the Retinitis Pigmentosa Protein RP2
    Houbin Zhang; Fiscal Year: 2010
    ..The project outlined in this proposal describes generation of an animal model mimicking this disease, attempting to unlock the secret behind this disease and search for clues for future potential treatment. ..
  44. Regulation Mechanisms for the GTPase activating protein domain of plexins
    Xuewu Zhang; Fiscal Year: 2013
    ..These studies together will reveal the molecular basis for the autoinhibition and activation of the plexin GAP domain, and provide new routes to future drug design for diseases associated with plexin malfunction. ..
  45. Molecular mechanisms of altered calcium sensing in human parathyroid disease
    John A Olson; Fiscal Year: 2013
    ....
  46. G protein regulation by monoubiquitination
    Henrik G Dohlman; Fiscal Year: 2013
    ..Our preliminary data reveal that monoubiquitinated Ras is refractory to GTPase activating proteins, but is otherwise fully functional...
  47. A myosin-like protein and GTPase required for gliding
    Patricia Hartzell; Fiscal Year: 2009
    ..Antibody and GFP-tagged proteins will be used to examine the interaction between MgIA and AglZ in vivo and in vitro. ..
  48. Clip R-59: a novel regulator of Akt signaling
    Keyong Du; Fiscal Year: 2013
    ....
  49. ARF regulators in endocytic transport
    Victor W Hsu; Fiscal Year: 2013
    ..This understanding will be broadly applicable to understanding human diseases, as many are now appreciated to arise because of defects in protein transport within the cell. ..
  50. Regulation of Memory Formation by the GTPase-activating Protein SynGAP
    Gavin R Rumbaugh; Fiscal Year: 2013
    ....
  51. Roles of MyoGEF in cytokinesis
    Qize Wei; Fiscal Year: 2011
    ....
  52. Coordination of membrane traffic through rab GEF and GAP cascades
    PETER JAY NOVICK; Fiscal Year: 2013
    ..guanine nucleotide exchange proteins (GEFs) that catalyze the displacement of GDP and binding of GTP and GTPase activating proteins (GAPs) that stimulate the slow intrinsic rate of GTP hydrolysis...
  53. Structural and Functional Studies of Galphaq and Its Signaling Complexes
    John J G Tesmer; Fiscal Year: 2013
    ..This knowledge is essential for understanding fundamental processes that underlie cardiac and neuromuscular function, and for developing new approaches to treat cardiovascular disease. ..
  54. Characterization of MWS/DEN, a novel regulator of amino acid signaling to mTORC1
    Lynne Chantranupong; Fiscal Year: 2013
    ..These insights may lead to the development of novel biomarkers and therapeutic strategies for cancer. ..
  55. Developing Small Molecule ARFGAP Regulators to Dissect Cell Signaling
    Qisheng Zhang; Fiscal Year: 2013
    ..Such perturbation is essential to understand the roles for ARFGAPs in diseases. In addition, the proposed research will establish a novel link between ARFGAPs and the Wnt/2-catenin signaling pathway. ..
  56. Regulation of Ras by Monoubiquitination
    Sharon L Campbell; Fiscal Year: 2013
    ..Mutationally activated Ras proteins are refractory to inactivation by GTPase activating proteins, and are persistently GTP- bound, leading to chronic downstream effectors activation and signaling...
  57. Mapping the Architecture of Cancer Signaling Pathways
    Scott H Soderling; Fiscal Year: 2010
    ..signaling switches" that are turned "on" or "off" by GEF (Guanine nucleotide Exchange Factors) and GAP (GTPase Activating Proteins) proteins. What is not known are the molecular mechanisms that determine Rho GEF and GAP specificity...
  58. Regulation of translation through the human translation initiation factor eIF5B
    ASSEN G MARINTCHEV; Fiscal Year: 2010
    ....
  59. Delivery of signaling and structural proteins to photoreceptor outer segment
    Vadim Y Arshavsky; Fiscal Year: 2013
    ..Elucidating these mechanisms is essential for developing strategies for disease prevention and future therapeutic interventions. ..
  60. PHEOCHROMOCYTOMAS FROM NEUROFIBROMATOSIS KNOCKOUT MICE
    Arthur Tischler; Fiscal Year: 2003
    ..4) To determine the status of neurofibromin in MPC cells and test the hypothesis that abnormal regulation of ras activity is responsible for neuronal differentiation in this model. ..
  61. G Protein-Coupled Receptors -- Structure and Regulation
    Elliott M Ross; Fiscal Year: 2013
    ..modules consist of a conserved group of interacting proteins: receptors, G protein Ga and Gbg subunits, GTPase activating proteins (GAP) and effector proteins...
  62. COPI Transport
    Victor W Hsu; Fiscal Year: 2013
    ..Moreover, because this basic process is critical for many cellular events, our results may also suggest new molecular insights into how multiple human diseases occur. ..
  63. GBeta5/RGS proteins and GPCR signaling
    JOHN E SONDEK; Fiscal Year: 2010
    ..It is anticipated that these studies will then be used to guide treatment regimens in cases where coordinated signaling mediated by R7 proteins has failed. ..
  64. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID CLAPP; Fiscal Year: 2001
    ..Mammalian GTPase activating proteins (GAPs) regulate Ras proteins by accelerating GTP hydrolysis...
  65. Identification of Drug Targets for NF1
    Yolanda Sanchez; Fiscal Year: 2010
    ..There is no better model than the yeast for these types of screens, thus by combining these two models we present a powerful approach for screening compounds to identify and validate potential drug targets for NF1. ..
  66. The role of Pak1 in regulating plexiform neurofibroma formation
    Andrew McDaniel; Fiscal Year: 2009
    ..Preventing or reducing the size of these tumors could increase quality of life for tens of thousands of affected individuals each year. ..
  67. NEUROFIBROMIN (Nf1) SIGNALING AND TARGET GENES IN OSTEOBLASTS
    Florent Elefteriou; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  68. Arabidopsis basil immunity to human and plant pathogens
    Sheng He; Fiscal Year: 2004
    ..abstract_text> ..
  69. Role of Rab GAPs AS160 and Tbc1d1 in GLUT4 translocation and glucose homeostasis
    SUSANNA KELLER; Fiscal Year: 2009
    ..It will further provide crucial information towards the validation of AS160 and Tbc1d1 as drug targets to improve glucose homeostasis and prevent ensuing complications of insulin resistance. ..
  70. Neurofibromin, Ras & NFAT in Cardiovascular Development
    FRAZ ISMAT; Fiscal Year: 2009
    ..Together this training program will prepare me for independent investigation, lead to a better understanding of cardiovascular abnormalities in neurofibromatosis, and address fundamental issues of cardiovascular development. ..