rac gtp binding proteins

Summary

Summary: A sub-family of RHO GTP-BINDING PROTEINS that is involved in regulating the organization of cytoskeletal filaments. This enzyme was formerly listed as EC 3.6.1.47.

Top Publications

  1. ncbi The small GTP-binding protein rac regulates growth factor-induced membrane ruffling
    A J Ridley
    Institute for Cancer Research, Chester Beatty Laboratories, London, England
    Cell 70:401-10. 1992
  2. ncbi Mammalian Rho GTPases: new insights into their functions from in vivo studies
    Sarah J Heasman
    Randall Division of Cell and Molecular Biophysics, King s College London, Guy s Campus, London, UK
    Nat Rev Mol Cell Biol 9:690-701. 2008
  3. ncbi A brain serine/threonine protein kinase activated by Cdc42 and Rac1
    E Manser
    Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge
    Nature 367:40-6. 1994
  4. pmc Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis
    Supriya Srinivasan
    Department of Cellular and Molecular Pharmacology and the Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA
    J Cell Biol 160:375-85. 2003
  5. ncbi Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion
    L Luo
    Howard Hughes Medical Institute, Department of Physiology, University of California at San Francisco 94143
    Genes Dev 8:1787-802. 1994
  6. ncbi Small GTP-binding proteins
    Y Takai
    Department of Molecular Biology, Osaka University Graduate School of Medicine Faculty of Medicine, Suita, Japan
    Physiol Rev 81:153-208. 2001
  7. ncbi Inhibition of myosin light chain kinase by p21-activated kinase
    L C Sanders
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 283:2083-5. 1999
  8. ncbi Regulation of NADPH oxidases: the role of Rac proteins
    Peter L Hordijk
    Department Molecular Cell Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Circ Res 98:453-62. 2006
  9. ncbi Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics
    D C Edwards
    Department of Chemistry, University of California at San Diego, La Jolla 92093 0650, USA
    Nat Cell Biol 1:253-9. 1999
  10. pmc Rational design and characterization of a Rac GTPase-specific small molecule inhibitor
    Yuan Gao
    Division of Experimental Hematology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 101:7618-23. 2004

Detail Information

Publications257 found, 100 shown here

  1. ncbi The small GTP-binding protein rac regulates growth factor-induced membrane ruffling
    A J Ridley
    Institute for Cancer Research, Chester Beatty Laboratories, London, England
    Cell 70:401-10. 1992
    ..We propose that rac and rho are essential components of signal transduction pathways linking growth factors to the organization of polymerized actin...
  2. ncbi Mammalian Rho GTPases: new insights into their functions from in vivo studies
    Sarah J Heasman
    Randall Division of Cell and Molecular Biophysics, King s College London, Guy s Campus, London, UK
    Nat Rev Mol Cell Biol 9:690-701. 2008
    ..The recent availability of knockout mice for several members of the Rho family reveals new information about their roles in signalling to the cytoskeleton and in development...
  3. ncbi A brain serine/threonine protein kinase activated by Cdc42 and Rac1
    E Manser
    Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge
    Nature 367:40-6. 1994
    ..This bimolecular interaction provides a model for studying p21 regulation of mammalian phosphorylation signalling pathways...
  4. pmc Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis
    Supriya Srinivasan
    Department of Cellular and Molecular Pharmacology and the Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA
    J Cell Biol 160:375-85. 2003
    ..We conclude that Rac plays a dominant role in the PI(3,4,5)P3-dependent positive feedback loop required for forming a leading edge, whereas location and stability of the leading edge are regulated by Cdc42...
  5. ncbi Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion
    L Luo
    Howard Hughes Medical Institute, Department of Physiology, University of California at San Francisco 94143
    Genes Dev 8:1787-802. 1994
    ..Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis...
  6. ncbi Small GTP-binding proteins
    Y Takai
    Department of Molecular Biology, Osaka University Graduate School of Medicine Faculty of Medicine, Suita, Japan
    Physiol Rev 81:153-208. 2001
    ..Cascades and cross-talks of small G proteins have also been clarified. In this review, functions of small G proteins and their modes of activation and action are described...
  7. ncbi Inhibition of myosin light chain kinase by p21-activated kinase
    L C Sanders
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 283:2083-5. 1999
    ..These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation...
  8. ncbi Regulation of NADPH oxidases: the role of Rac proteins
    Peter L Hordijk
    Department Molecular Cell Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Circ Res 98:453-62. 2006
    ..This review focuses on the role of the Rac1 and Rac2 GTPases in the activation of the various NOX family members...
  9. ncbi Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics
    D C Edwards
    Department of Chemistry, University of California at San Diego, La Jolla 92093 0650, USA
    Nat Cell Biol 1:253-9. 1999
    ..A Pak1-specific inhibitor, corresponding to the Pak1 autoinhibitory domain, blocks LIM-kinase-induced cytoskeletal changes. Activated GTPases can thus regulate actin depolymerization through Pak1 and LIM-kinase...
  10. pmc Rational design and characterization of a Rac GTPase-specific small molecule inhibitor
    Yuan Gao
    Division of Experimental Hematology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 101:7618-23. 2004
    ..Thus, NSC23766 constitutes a Rac-specific small-molecule inhibitor that could be useful to study the role of Rac in various cellular functions and to reverse tumor cell phenotypes associated with Rac deregulation...
  11. pmc The small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell-cell contacts
    V M Braga
    Medical Research Council Laboratory for Molecular Cell Biology, University College London, WC1E 6BT, London, United Kingdom
    J Cell Biol 137:1421-31. 1997
    ..Our results provide new insights into the role of the small GTPases in the cadherin-dependent cell- cell contact formation and the remodelling of actin filaments in epithelial cells...
  12. ncbi Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells
    B Wojciak-Stothard
    Ludwig Institute for Cancer Research, London, United Kingdom
    J Cell Physiol 176:150-65. 1998
    ..Our data suggest that Cdc42, Rac, and Rho are activated in a hierarchical cascade following stimulation with TNF-alpha leading to actomyosin-mediated cell retraction and formation of intercellular gaps...
  13. ncbi P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac
    Heidi C E Welch
    Inositide Laboratory, Cambridge CB2 4AT, United Kingdom
    Cell 108:809-21. 2002
    ..P-Rex1 appears to be a coincidence detector in PtdIns(3,4,5)P3 and Gbetagamma signaling pathways that is particularly adapted to function downstream of heterotrimeric G proteins in neutrophils...
  14. ncbi Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans
    Jason M Kinchen
    Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11743, USA
    Nature 434:93-9. 2005
    ....
  15. ncbi Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K
    P J Keely
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599 7365, USA
    Nature 390:632-6. 1997
    ..PI(3)K inhibition also disrupts actin structures, suggesting that activation of PI(3)K by Cdc42 and Rac1 alters actin organization, leading to increased motility and invasiveness...
  16. ncbi C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180
    Y C Wu
    Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 392:501-4. 1998
    ..We name this new family of proteins that function in the extension of cell surfaces the CDM (for CED-5, DOCK180 and MBC) family...
  17. ncbi PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1
    Takashi Nishimura
    Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi 466 8550, Japan
    Nat Cell Biol 7:270-7. 2005
    ..We propose that the PAR-6-PAR-3 complex mediates Cdc42-induced Rac activation by means of STEF/Tiam1, and that this process seems to be required for the establishment of neuronal polarity...
  18. pmc Rho GTPases and their effector proteins
    A L Bishop
    MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, U K
    Biochem J 348:241-55. 2000
    ..The main focus of this review will be Rho, Rac and Cdc42, the three best characterized mammalian Rho GTPases, though the genetic analysis of Rho GTPases in lower eukaryotes is making increasingly important contributions to this field...
  19. ncbi Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense
    A W Roberts
    Howard Hughes Medical Institute, and Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202, USA
    Immunity 10:183-96. 1999
    ..Rac2 is an essential regulator of multiple specialized neutrophil functions...
  20. ncbi The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF
    C S Hill
    Transcription Laboratory, Imperial Cancer Research Fund Laboratories, London, England
    Cell 81:1159-70. 1995
    ..Functional Rho is required for regulated activity of the c-fos promoter. These results establish SRF as a nuclear target of a novel Rho-mediated signaling pathway...
  21. ncbi Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis
    Erik Sahai
    Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK
    Nat Cell Biol 5:711-9. 2003
    ..Combined blockade of extracellular proteases and ROCK negates the ability of tumour cells to switch between modes of motility and synergises to prevent tumour cell invasion...
  22. ncbi Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration
    Shiro Suetsugu
    Department of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo, 108 8639, Japan
    Dev Cell 5:595-609. 2003
    ..Thus, WAVE2 is essential for leading edge extension for directed migration in general and WAVE1 is essential in MMP-dependent migration in ECM...
  23. ncbi Rho and Rac take center stage
    Keith Burridge
    Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Cell 116:167-79. 2004
    ..Additionally, we will discuss how there is signaling crosstalk between family members and how various bacterial pathogens have developed strategies to manipulate Rho protein activity so as to enhance their own survival...
  24. ncbi A role for Rac in Tiam1-induced membrane ruffling and invasion
    F Michiels
    The Netherlands Cancer Institute, Division of Cell Biology, Amsterdam
    Nature 375:338-40. 1995
    ..Moreover, T-lymphoma cells expressing V12Rac1 become invasive, indicating that the Tiam1-Rac signalling pathway could be operating in the invasion and metastasis of tumour cells...
  25. ncbi E-cadherin homophilic ligation directly signals through Rac and phosphatidylinositol 3-kinase to regulate adhesive contacts
    Eva M Kovacs
    Department of Physiology and Pharmacology, School of Biomedical Science, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
    J Biol Chem 277:6708-18. 2002
    ..We propose that a key function of these cadherin-activated signals is to control adhesive contacts, probably via regulation of the actin cytoskeleton, which ultimately serves to mediate adhesive cell-cell recognition...
  26. ncbi Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells
    M A Sells
    Fox Chase Cancer Centre, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA
    Curr Biol 7:202-10. 1997
    ..This kinase is therefore a candidate effector for the changes in cell shape induced by growth factors...
  27. ncbi Stem cell depletion through epidermal deletion of Rac1
    Salvador Aznar Benitah
    Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Science 309:933-5. 2005
    ..We conclude that a pleiotropic regulator of cell adhesion and the cytoskeleton plays a critical role in controlling exit from the stem cell niche and propose that Rac and Myc represent a global stem cell regulatory axis...
  28. pmc Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes
    E Manser
    Glaxo IMCB Group, Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge
    Mol Cell Biol 17:1129-43. 1997
    ..These data support our previous suggestions of a role for PAK downstream of both Cdc42 and Rac1 and indicate that PAK functions include the dissolution of stress fibers and reorganization of focal complexes...
  29. ncbi Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12
    Xiaochen Wang
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Science 302:1563-6. 2003
    ..Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis...
  30. pmc Activation of Rac1 by a Crk SH3-binding protein, DOCK180
    E Kiyokawa
    Department of Pathology, National Institute of Infectious Diseases, Toyama, Shinjuku ku, Tokyo 162 8640, Japan
    Genes Dev 12:3331-6. 1998
    ..Dominant-negative Rac1 suppressed DOCK180-induced membrane spreading. These results strongly suggest that DOCK180 is a novel activator of Rac1 and involved in integrin signaling...
  31. ncbi Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav
    J Han
    Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033 0800, USA
    Science 279:558-60. 1998
    ..Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac...
  32. ncbi Rac function and regulation during Drosophila development
    Satoko Hakeda-Suzuki
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Nature 416:438-42. 2002
    ..Different Rac activators thus act in different developmental processes. The specific cellular response to Rac activation may be determined more by the upstream activator than the specific Rac protein involved...
  33. ncbi Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle
    A Mettouchi
    Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 8:115-27. 2001
    ..This process is mediated by SOS and PI-3K and requires coordinate upstream signals through Shc and FAK. These results indicate that Rac is a crucial mediator of the integrin-specific control of cell cycle in endothelial cells...
  34. ncbi Regulation of innate immunity by Rho GTPases
    Gary M Bokoch
    Department of Immunology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Trends Cell Biol 15:163-71. 2005
    ..An understanding of the biochemical basis for such distinct activities should provide novel insights into the molecular details of Rho GTPase function and regulation in innate immunity...
  35. pmc A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways
    Y Horii
    Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    EMBO J 13:4776-86. 1994
    ..Of the tissues examined, expression of ost was the highest in brain and could be localized to neurons and alpha-tanycytes, suggesting that Ost may participate in axonal transport in these specialized cells...
  36. pmc Ras family GTPases control growth of astrocyte processes
    D Kalman
    Department of Microbiology and Immunology, G W Hooper Foundation Laboratories, University of California at San Francisco, San Francisco, California 94143, USA
    Mol Biol Cell 10:1665-83. 1999
    ....
  37. ncbi Sphingosine-1-phosphate, a platelet-derived lysophospholipid mediator, negatively regulates cellular Rac activity and cell migration in vascular smooth muscle cells
    Yasuji Ryu
    Department of Physiology, Kanazawa University, Graduate School of Medicine, Kanazawa, Ishikawa, Japan
    Circ Res 90:325-32. 2002
    ..These results together indicate that Edg isoform-specific, negative or positive regulation of cellular Rac activity is critically involved in S1P-mediated bimodal regulation of cell motility in SMCs and HUVECs...
  38. pmc Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane
    Tomoyo Okada
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Cell Biol 171:361-71. 2005
    ..These results provide a framework for understanding the tumor suppressor function of Merlin and indicate that Merlin mediates contact inhibition of growth by suppressing recruitment of Rac to matrix adhesions...
  39. ncbi Functions of Rac GTPases during neuronal development
    Ivan de Curtis
    Cell Adhesion Unit, San Raffaele Scientific Institute, Milan, Italy
    Dev Neurosci 30:47-58. 2008
    ....
  40. ncbi Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila
    T P Newsome
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 101:283-94. 2000
    ..We propose that distinct signals transduced via Trio and Dock act combinatorially to activate Pak in spatially restricted domains within the growth cone, thereby controlling the direction of axon extension...
  41. 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...
  42. ncbi Rac activation and inactivation control plasticity of tumor cell movement
    Victoria Sanz-Moreno
    Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK
    Cell 135:510-23. 2008
    ..We demonstrate tight interplay between Rho and Rac in determining different modes of tumor cell movement, revealing how tumor cells switch between different modes of movement...
  43. ncbi Rac1 signalling in the Drosophila larval cellular immune response
    Michael J Williams
    Umeå Centre for Molecular Pathogenesis UCMP, Umea University, S 901 87, Umea, Sweden
    J Cell Sci 119:2015-24. 2006
    ..From these data we conclude that Rac1 induces Bsk activity and stable actin formation for cellular immune activation, leading to sessile hemocyte release and an increase in the number of circulating hemocytes...
  44. ncbi Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass
    Chun Xiang Sun
    Faculty of Dentistry, University of Toronto, Rm 241, 150 College St, Toronto, ON, Canada M5S 1A8
    Blood 104:3758-65. 2004
    ....
  45. 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...
  46. ncbi Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways
    Julien Cau
    MRC Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London
    J Cell Sci 118:2579-87. 2005
    ..We conclude that in migrating cells, Cdc42 co-ordinately regulates the polarity of the microtubule and actin cytoskeletons through two distinct pathways...
  47. ncbi Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization
    N Yang
    Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
    Nature 393:809-12. 1998
    ..Furthermore, insulin and an active form of Rac increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1 participates in Rac-mediated actin cytoskeletal reorganization, probably by phosphorylating cofilin...
  48. ncbi Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells
    Sandra van Wetering
    Department of Experimental Immunohematology, Academic Medical Center, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands
    J Cell Sci 115:1837-46. 2002
    ....
  49. ncbi Activation of phosphoinositide 3-OH kinase by the alpha6beta4 integrin promotes carcinoma invasion
    L M Shaw
    Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell 91:949-60. 1997
    ..The small G protein Rac is required downstream of PI3K for invasion. These studies define a mechanism by which the alpha6beta4 integrin promotes carcinoma invasion and invoke a novel function for PI3K signaling...
  50. ncbi Integrin signaling to the actin cytoskeleton
    Kris A DeMali
    Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Curr Opin Cell Biol 15:572-82. 2003
    ..Integrins promote actin assembly via the recruitment of molecules that directly activate the actin polymerization machinery or physically link it to sites of cell adhesion...
  51. ncbi Rho GTPases are over-expressed in human tumors
    G Fritz
    Institute of Toxicology, Division of Applied Toxicology, University of Mainz, Germany
    Int J Cancer 81:682-7. 1999
    ..Overall, increase in the amount of Rho GTPases, in particular RhoA, appears to be a frequent event in different types of human tumors. This supports the view that Rho GTPases are involved in human carcinogenesis...
  52. pmc Synapse formation is regulated by the signaling adaptor GIT1
    Huaye Zhang
    Department of Cell Biology, University of Virginia, Charlottesville, VA 22908 0732, USA
    J Cell Biol 161:131-42. 2003
    ....
  53. 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
    ..These results suggest that GEF-H1 may have a direct role in activation of Rac and/or Rho and in bringing the activated GTPase to specific target sites such as microtubules...
  54. pmc A Rac switch regulates random versus directionally persistent cell migration
    Roumen Pankov
    Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 170:793-802. 2005
    ..Total Rac1 activity can therefore provide a regulatory switch between patterns of cell migration by a mechanism distinct from chemotaxis...
  55. ncbi Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency
    D A Williams
    Department of Pediatrics, Wells Center for Pediatric Research, Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, IN 46202 5225, USA
    Blood 96:1646-54. 2000
    ..Blood. 2000;96:1646-1654)..
  56. pmc Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein family
    T H Chuang
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 92:10282-6. 1995
    ..These data suggest the multifunctional Bcr and Abr proteins might interact simultaneously and/or sequentially with members of the Rho family to regulate and coordinate cellular signaling...
  57. ncbi Rho family GTPases bind to phosphoinositide kinases
    K F Tolias
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    J Biol Chem 270:17656-9. 1995
    ....
  58. pmc Effects of cell tension on the small GTPase Rac
    Akira Katsumi
    Division of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Cell Biol 158:153-64. 2002
    ..We hypothesize that regulation of Rac activity by tension may be important for motility, polarization, and directionality of cell movement...
  59. ncbi Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells
    Shusaku Kurisu
    Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Oncogene 24:1309-19. 2005
    ..Thus, WAVE2 acts as the primary effector downstream of Rac to achieve invasion and metastasis, suggesting that suppression of WAVE2 activity holds a promise for preventing cancer invasion and metastasis...
  60. pmc Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation
    D R Ambruso
    Bonfils Blood Center, Denver, CO 80220, USA
    Proc Natl Acad Sci U S A 97:4654-9. 2000
    ..These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome...
  61. pmc Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis
    Kersi N Pestonjamasp
    Departments of Immunology and Cell Biology IMM14, The Scripps Research Institute, La Jolla, CA, USA
    Blood 108:2814-20. 2006
    ..We conclude that Rac plays both positive and negative roles in the organization of the Rhomyosin "backness" program, thereby promoting stable polarity in chemotaxing neutrophils...
  62. ncbi Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome
    P Aspenstrom
    Department of Zoological Cell Biology, Wenner Gren Institute, Stockholm, Sweden
    Curr Biol 6:70-5. 1996
    ..In order to examine more closely the mechanisms underlying the diverse functions of Rho GTPases in mammalian cells, we searched for downstream targets of these proteins...
  63. pmc ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts
    Takahiro Tsuji
    Department of Pharmacology, Kyoto University Faculty of Medicine, 606 8501, Japan
    J Cell Biol 157:819-30. 2002
    ..Thus, these results have revealed the Rho-dependent Rac activation signaling that is mediated by mDia1 through Cas phosphorylation and antagonized by the action of ROCK...
  64. ncbi CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans
    P W Reddien
    Howard Hughes Medical Institute, Department of Biology, 68 425, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Cell Biol 2:131-6. 2000
    ..We propose that CED-2/CrkII and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces...
  65. ncbi The Rac exchange factor Tiam1 is required for the establishment and maintenance of cadherin-based adhesions
    Angeliki Malliri
    Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Biol Chem 279:30092-8. 2004
    ..These studies indicate that the Rac activator Tiam1 is essential for the formation as well as the maintenance of cadherin-based adhesions...
  66. pmc Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the integrin alpha4beta1
    David García-Bernal
    Department of Immunology, Centro de Investigaciones Biologicas, CSIC, 28006 Madrid, Spain
    Mol Biol Cell 16:3223-35. 2005
    ..These results indicate that activation of Vav1-Rac signaling pathway by CXCL12 represents an important inside-out event controlling efficient up-regulation of alpha4beta1-dependent T lymphocyte adhesion...
  67. pmc Deficiency of small GTPase Rac2 affects T cell activation
    H Yu
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Exp Med 194:915-26. 2001
    ..The phenotypic similarity of Rac2(-/-) to Vav(-/-) cells implicates Rac2 as a downstream mediator of Vav signaling...
  68. ncbi Pak to the future
    S Bagrodia
    Dept of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 6401, USA
    Trends Cell Biol 9:350-5. 1999
    ..We present these recent findings and consider how these new regulators and targets could explain some of the cellular effects that have been attributed to Pak family members...
  69. ncbi Genetic ablation of Rac1 in cartilage results in chondrodysplasia
    Guoyan Wang
    CIHR Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada
    Dev Biol 306:612-23. 2007
    ..In summary, these data identify a novel, essential and tissue-specific role of Rac1 in skeletal development and demonstrate that Rac1 deficiency affects numerous regulatory pathways in cartilage...
  70. ncbi Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation
    B Li
    Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520 8011, USA
    Science 288:2219-22. 2000
    ..Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression...
  71. pmc Rac activation: P-Rex1 - a convergence point for PIP(3) and Gbetagamma?
    Orion D Weiner
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave C 1, 502, Boston, Massachusetts 02115, USA
    Curr Biol 12:R429-31. 2002
    ..P-Rex1 is synergistically activated by PIP(3) and Gbetagamma and may act as a coincidence detector for these signaling molecules...
  72. ncbi Rho family GTP-binding proteins in growth cone signalling
    L Luo
    Howard Hughes Medical Institute, Department of Physiology, University of California at San Francisco, California 94143, USA
    Curr Opin Neurobiol 7:81-6. 1997
    ..Recent evidence suggests that they may also be important components of the signalling pathways that link the reception of extracellular cues to the regulation of the cytoskeleton in neuronal growth cones...
  73. ncbi Phosphoinositide 3-kinase-dependent activation of Rac
    Heidi C E Welch
    Inositide Laboratory, Signalling Programme, The Babraham Institute, Cambridge CB2 4AT, UK
    FEBS Lett 546:93-7. 2003
    ..Vice versa, Rac can also stimulate the activation of PI3K, although the mechanism for this is unclear. We review here the evidence that links PI3K and Rac signalling pathways...
  74. ncbi DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1
    Terukazu Sanui
    Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Blood 102:2948-50. 2003
    ....
  75. ncbi Drosophila melanogaster Rac2 is necessary for a proper cellular immune response
    Michael J Williams
    Umea Centre for Molecular Pathogenesis, Umea University, S 901 87 Umea, Sweden
    Genes Cells 10:813-23. 2005
    ..Finally, larger cells known as lamellocytes attach to the capsule but also fail to spread, and there is a lack of melanization. From these results it appears that Rac2 is necessary for the larval cellular immune response...
  76. ncbi P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration
    Ivette Hernández-Negrete
    Department of Pharmacology, CINVESTAV IPN, Apartado Postal 14 740, Mexico DF, 07000 Mexico
    J Biol Chem 282:23708-15. 2007
    ..mTORC2 has been described as the catalytic complex that phosphorylates AKT/PKB at Ser-473 and elicits activation of Rho GTPases and cytoskeletal reorganization. Thus, P-Rex1 links mTOR signaling to Rac activation and cell migration...
  77. ncbi Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin
    Bertram Canagarajah
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892, USA
    Cell 119:407-18. 2004
    ..Phospholipid binding to the C1 domain triggers the cooperative dissociation of these interactions, allowing the N terminus to move out of the active site and thereby activating the enzyme...
  78. pmc CAS/Crk coupling serves as a "molecular switch" for induction of cell migration
    R L Klemke
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Cell Biol 140:961-72. 1998
    ..Thus, CAS/Crk assembly serves as a "molecular switch" for the induction of cell migration and appears to contribute to the invasive property of tumors...
  79. ncbi Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex
    Enrico Brugnera
    Beirne Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA
    Nat Cell Biol 4:574-82. 2002
    ..We can also detect a trimeric ELMO1 Dock180 Rac1 complex and ELMO augments the interaction between Dock180 and Rac. We propose that the Dock180 ELMO complex functions as an unconventional two-part exchange factor for Rac...
  80. ncbi Plexin-B semaphorin receptors interact directly with active Rac and regulate the actin cytoskeleton by activating Rho
    M H Driessens
    MRC Laboratory for Molecular Cell Biology, Department of Biochemistry and Molecular Biology, University College London, London, WC1E 6BT, United Kingdom
    Curr Biol 11:339-44. 2001
    ..Our findings that plexin-B signaling to the cytoskeleton is both Rac and Rho dependent form a starting point for unraveling the mechanism by which semaphorins and plexins control axon guidance and cell migration...
  81. ncbi Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity
    D Diekmann
    Medical Research Council Laboratory for Molecular Cell Biology, University College London, UK
    Science 265:531-3. 1994
    ..Modified forms of Rac with mutations in the effector site did not stimulate oxidase activity or bind to p67phox. Thus, p67phox appears to be the Rac effector protein in the NADPH oxidase complex...
  82. ncbi A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases
    P D Burbelo
    Medical Research Council Laboratory for Molecular Cell Biology, University College London, United Kingdom
    J Biol Chem 270:29071-4. 1995
    ..These results indicate that proteins containing the CRIB motif bind to Cdc42 and/or Rac in a GTP-dependent manner, and they may, therefore, participate in downstream signaling...
  83. pmc Rac inhibition reverses the phenotype of fibrotic fibroblasts
    Shi wen Xu
    Centre for Rheumatology, Department of Medicine, University College London Royal Free Campus, London, United Kingdom
    PLoS ONE 4:e7438. 2009
    ..The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies...
  84. ncbi The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1
    Lorraine C Santy
    Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, USA
    Curr Biol 15:1749-54. 2005
    ..Together, these data suggest that ARNO and ARF6 coordinate with the Dock180/Elmo complex to promote Rac activation at the leading edge of migrating cells...
  85. ncbi Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits
    Kirsti Hill
    Inositide Laboratory, The Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, United Kingdom
    J Biol Chem 280:4166-73. 2005
    ....
  86. pmc Defective Rac-mediated proliferation and survival after targeted mutation of the beta1 integrin cytodomain
    Emilio Hirsch
    Dipartimento di Genetica, Biologia, e Biochimica, Universita di Torino, 10126 Torino, Italy
    J Cell Biol 157:481-92. 2002
    ..Altogether, our data provide the evidence for an epistatic interaction between the beta1 integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control...
  87. ncbi CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein
    Annette Schenck
    Department of Molecular Pathology, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP, Boite Postale 10142, 67404 Illkirch, Cedex, France
    Neuron 38:887-98. 2003
    ..CYFIP interacts biochemically and genetically with dFMR1 and dRac1. Finally, CYFIP acts as a dRac1 effector that antagonizes FMR1 function, providing a bridge between signal-dependent cytoskeleton remodeling and translation...
  88. ncbi Redox-dependent downregulation of Rho by Rac
    Anjaruwee S Nimnual
    Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
    Nat Cell Biol 5:236-41. 2003
    ..Our findings define a novel mechanism for the coupling of changes in cellular redox state to the control of actin cytoskeleton rearrangements by Rho GTPases...
  89. ncbi Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO
    Colin D deBakker
    Department of Microbiology, Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA
    Curr Biol 14:2208-16. 2004
    ..However, the components upstream of ELMO and Dock180 during engulfment remain elusive...
  90. ncbi Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis
    Elisabeth M Gardiner
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Biol 12:2029-34. 2002
    ..These data establish that Rac GTPase is spatially and temporally regulated to coordinate leading-edge extension and tail retraction during a complex motile response, the chemotaxis of human neutrophils...
  91. ncbi Regulation of cancer cell motility through actin reorganization
    Daisuke Yamazaki
    Department of Biochemistry, Institute of Medical Science, University of Tokyo, Minato ku, Japan
    Cancer Sci 96:379-86. 2005
    ..Inhibition of Rho family small GTPase signaling suppresses the migration and invasion of cancer cells. Thus, control of cell migration via the actin cytoskeleton provides the possibility of regulating cancer cell invasion and metastasis...
  92. ncbi Rac2 stimulates Akt activation affecting BAD/Bcl-XL expression while mediating survival and actin function in primary mast cells
    F C Yang
    Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202, USA
    Immunity 12:557-68. 2000
    ..These results suggest that Rac2 plays a unique role in multiple cellular functions and describe an essential role for Rac2 in growth factor-dependent survival and expression of BAD/Bcl-XL...
  93. pmc Rac1 expression by fibroblasts is required for tissue repair in vivo
    Shangxi Liu
    Department of Physiology and Pharmacology, Division of Oral Biology, Schulich School of Medicine and Dentistry, Canadian Institute of Health Research Group in Skeletal Development and Remodeling, University of Western Ontario, London, Ontario, Canada
    Am J Pathol 174:1847-56. 2009
    ..Thus, Rac1 is an essential signaling integrator that is required for normal wound healing and dermal homeostasis...
  94. pmc Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics
    Anjana Nayal
    Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA
    J Cell Biol 173:587-9. 2006
    ..These adhesions appear to be regulated by the GIT1-PIX-PAK module near the leading edge...
  95. pmc Efficient dendritic cell priming of T lymphocytes depends on the extracellular matrix protein mindin
    Hong Li
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    EMBO J 25:4097-107. 2006
    ..These results suggest that mindin-integrin interactions play a key role in regulating Rho GTPase expression in DCs and DC priming of T lymphocytes...
  96. ncbi Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase
    Celine DerMardirossian
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 15:117-27. 2004
    ..These results support a role for Pak1-mediated RhoGDI phosphorylation as a mechanism for Cdc42-mediated Rac activation, and suggest the possibility of Rac-induced positive feed-forward regulation of Rac activity...
  97. pmc A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins
    M Agnel
    Laboratoire de Génétique et Biologie Cellulaires, Centre National de la Recherche Scientifique, Marseille, France
    Mol Cell Biol 12:5111-22. 1992
    ..In addition to being expressed in the imaginal discs, the m1.7 racGAP transcript was detected in developmentally specific germ line cells of the testes, the primary spermatocytes...
  98. pmc Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila
    S Eaton
    Programme in Cell Biology, European Molecular Biology Laboratory, Heidelberg, Germany
    J Cell Biol 135:1277-89. 1996
    ..During hair formation, the apical microtubules that point distally elongate and fill the emerging wing hair. As the hair elongates, junctional proteins are reorganized on the proximal and distal edges of each cell...
  99. pmc Molecular requirements for actin-based lamella formation in Drosophila S2 cells
    Stephen L Rogers
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94107, USA
    J Cell Biol 162:1079-88. 2003
    ..Our results have identified an essential set of proteins involved in actin dynamics during lamella formation in Drosophila S2 cells...
  100. pmc RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs
    C Gauthier-Rouviere
    IGMM, CNRS UMR5535, route de Mende, 34293 Montpellier Cedex 05 France
    Mol Biol Cell 9:1379-94. 1998
    ..Therefore, our data demonstrate that RhoG controls a pathway that requires the microtubule network and activates Rac1 and Cdc42Hs independently of their growth factor signaling pathways...
  101. ncbi The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue
    M Hirshberg
    Division of Protein Structure, National Institute for Medical Research, Mill Hill, London, UK
    Nat Struct Biol 4:147-52. 1997
    ..38 A. Comparison with the structure of H-ras indicates that rac1 has an extra alpha-helical domain that is characteristic of the rho G proteins, and may be involved in the signalling pathway of this family...

Research Grants64

  1. HTS For Inhibitors of NADPH Oxidase 1 (Nox1)
    Gary Bokoch; Fiscal Year: 2008
    ..Such inhibitors will be useful to investigate Nox1 biology, and as potential therapeutic agents in inflammatory diseases and cancer. [unreadable] [unreadable] [unreadable]..
  2. REGULATION OF NEUTROPHIL RECEPTOR G PROTEIN INTERACTIONS
    Gary Bokoch; Fiscal Year: 2009
    ..Spatio-temporal evaluation of Rho activation will be related to Rac2 activity, as well as specific aspects of a) chemoattractant receptor signaling, b) motile behavior, and c) actin-myosin cytoskeletal dynamics. ..
  3. CONTROL OF PHAGOCYTE NADPH OXIDASE BY CYTOSOLIC PROTEINS
    Gary Bokoch; Fiscal Year: 2005
    ....
  4. RhoH GTPase in blood cell and cancer development
    Yi Gu; Fiscal Year: 2006
    ..Given the lineage-restricted expression of RhoH such an observation could have important therapeutic implication. ..
  5. Role of Vav family proteins in cell signaling and cancer
    XOSE BUSTELO; Fiscal Year: 2009
    ..abstract_text> ..
  6. STRUCTURE/FUNCTION ANALYSIS OF PHAGOCYTE PROTEINS
    Mary Dinauer; Fiscal Year: 2009
    ..These studies will provide further insight into the superoxide- generating system of the phagocyte, which may lead to new approaches in modulating superoxide formation in the inflammatory response and host defense. ..
  7. Role of Prostaglandins & Phospholipase A in melanocytes
    Glynis Scott; Fiscal Year: 2009
    ..We hypothesize that PG and phospholipases stimulate HM dendricity, MS transfer &pigmentation through different mechanisms that act synergistically to modulate cutaneous pigmentation following UVR. ..
  8. Role of Synaptojanin 2 in Tumor Cell Invasion
    Marc Symons; Fiscal Year: 2009
    ..The molecular analysis of the functions of SJ2 in the formation of lamellipodia and invadopodia and tumor cell migration and invasion will significantly expand our current understanding of the role of Rac1 in malignant transformation. ..
  9. Rho GtPase and Cell Cycle Regulation in Breast Cancer
    Catherine Welsh; Fiscal Year: 2005
    ..Welsh's progression to the status of independent investigator. ..
  10. Identification of RhoGEFs as novel therapeutic targets for malignant glioma
    Marc Symons; Fiscal Year: 2008
    ..We also expect that we will obtain significant clinical information that will aid in the validation of these invasion genes. [unreadable] [unreadable] [unreadable] [unreadable]..
  11. 2005 Phagocytes Gordon Conference
    Mary Dinauer; Fiscal Year: 2005
    ..The program will provide opportunities for participation of scientists at all levels and we will particularly promote the participation of junior investigators, postdoctoral trainees and "new investigators to the field". ..
  12. Mechanochemical regulation of endothelial permeability
    Konstantin Birukov; Fiscal Year: 2007
    ....
  13. Wnt Proteins During Intestinal Repair and Regeneration
    Calvin Kuo; Fiscal Year: 2009
    ....
  14. 2008 NOX Family NADPH Oxidases Gordon Conference
    WILLIAM NAUSEEF; Fiscal Year: 2008
    ..End of Abstract) [unreadable] [unreadable] [unreadable]..
  15. Biosynthesis, structural organization, and function of NOX proteins
    WILLIAM NAUSEEF; Fiscal Year: 2007
    ..abstract_text> ..
  16. Inhibitory Signaling via FcgRIIB Receptor on B Cells
    Kodi Ravichandran; Fiscal Year: 2008
    ....
  17. Apoptotic Cell Recognition & Clearance 2007 Gordon Research Conference
    Kodi Ravichandran; Fiscal Year: 2007
    ..The meeting is purposely held in alternative years with[unreadable] the Apoptosis meeting to encourage participation by all of those with an interest in cell death. ..
  18. Role of integrin signaling in gonad functions
    Myeongwoo Lee; Fiscal Year: 2007
    ..These studies will additionally advance our knowledge on the role of cell-ECM interaction in gonad development and functions. ..
  19. Regulation of CNS Angiogenesis By GPR124
    Calvin Kuo; Fiscal Year: 2009
    ..Finally, conditional approaches to GPR124 inactivation will be pursued using adenoviral and conditional knockout strategies, to facilitate the eventual study of GPR124 function in fully adult organisms. ..
  20. The Role of Rho GTPases in Ethanol-Induced Liver Injury
    Courtney Schaffert; Fiscal Year: 2007
    ..Our studies have begun to characterize how alcohol impairs these functions. Thus, results from the proposed research could lead to effective treatment strategies in alcoholic liver disease. [unreadable] [unreadable] [unreadable]..
  21. Phagocytosis of apoptotic cells: Signaling via GULP
    Kodi Ravichandran; Fiscal Year: 2007
    ..In these mouse studies, we will determine the effect on engulfment due to the absence of GULP, or disrupted GULP function, and any potential effects on autoimmunity due to defective engulfment. ..
  22. Inverted two photon laser scanning microscope for host defense
    Michael Dustin; Fiscal Year: 2008
    ..The impact on public health will be to develop better strategies to fight infections and reduce the incidence of pathogen triggered autoimmunity. [unreadable] [unreadable] [unreadable]..
  23. Protein Prenyltransferases in Glucose-Stimulated Insulin Secretion
    Anjaneyulu Kowluru; Fiscal Year: 2010
    ....
  24. Versatile scaffolds to visualize endogenous protein activation in living cells
    KLAUS MICHAEL HAHN; Fiscal Year: 2010
    ..PAK, JNK, and ERK2 are each on a different, parallel pathway downstream of Src. The spatio-temporal regulation of this signaling network to produce different cellular responses will be examined. ..
  25. Modulation of Host Cell Functions by Coxiella burnetii
    Craig R Roy; Fiscal Year: 2010
    ..These studies will elucidate pathogenic determinants that allow host cell infection by Coxiella and reveal intracellular infection strategies employed by this important pathogen. ..
  26. Lipid Raft Microdomains in Neutrophil Function
    ROBERT GARY SITRIN; Fiscal Year: 2010
    ..Hopefully, targeting the function of lipid raft microdomains will engender new therapeutic strategies for enhancing antimicrobial defenses and suppressing the deleterious effects of acute inflammation. ..
  27. Immunoreceptors
    Michael Dustin; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  28. The Role of CBFb-MYH11 in Acute Myeloid Leukemia
    James C Mulloy; Fiscal Year: 2010
    ..To identify specific signals that will cooperate in the transformation to acute leukemia, defined eenetic elements and saturatine retroviral mutaeenesis will be used. ..
  29. Reactive Oxygen Species in Anti-Viral Airway Host Defense
    Jeffrey Friedman; Fiscal Year: 2008
    ..Our studies will show if oxidases are a promising target for therapeutic drug development. [unreadable] [unreadable] [unreadable] [unreadable]..
  30. ERM and Rho Signal Pathways in T Cell Immune Senescence
    GONZALO GARCIA; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  31. Signaling by p21-activated protein kinases
    JONATHAN D CHERNOFF; Fiscal Year: 2010
    ....
  32. Specific Biochemical Inactivation of Oncogenic Ras
    Jeffrey Settleman; Fiscal Year: 2008
    ..Together, the proposed studies are expected to lead to the eventual development of a novel therapeutic approach for achieving specific targeting of human tumors that harbor oncogenic mutant forms of Ras. ..
  33. Spatial regulation of Protein Kinase A in cell migration
    Alan K Howe; Fiscal Year: 2010
    ..abstract_text> ..
  34. Chemokine Receptor Chimeras by Synthetic Gene Library
    Michael Dustin; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  35. Dynamics of MAPK Phosphorylation in Living Cells
    Klaus Hahn; Fiscal Year: 2004
    ..The fundamental processes controlled by Erk, including motility, apoptosis, and proliferation, are critical to normal homeostasis and relevant to many diseases and immune function. ..
  36. REGULATION OF P21-ACTIVATED KINASES
    Jonathan Chernoff; Fiscal Year: 2004
    ..Understanding the molecular basis for this regulation is not only of intrinsic scientific interest but is also likely to be relevant to important human diseases such as metastatic cancer. ..
  37. The NF2 gene: elucidation of tumor suppressor function
    JOSEPH KISSIL; Fiscal Year: 2004
    ..This should lead to a better understanding of merlin function in normal cells and the consequences of its loss in tumor development. Such information will directly assist in the search for effective therapies. ..
  38. ROLE OF PROTEIN PHOSPHATASES IN INSULIN SECRETION
    Anjaneyulu Kowluru; Fiscal Year: 2004
    ....
  39. The Urokinase-CD87 System in Macrophage Activation
    Robert Sitrin; Fiscal Year: 2004
    ....
  40. RHO GTPASE SIGNALING IN EMBRYO MORPHOGENESIS
    Jeffrey Settleman; Fiscal Year: 2003
    ..abstract_text> ..
  41. PKC Theta--A Novel Drug Target in T Cell Leukemias
    Amnon Altman; Fiscal Year: 2003
    ..abstract_text> ..
  42. Pruning of Motor Neuronal Arbors
    Joyce Fernandes; Fiscal Year: 2003
    ..These studies will have implications for better understanding the neurodevelopmental basis of diseases such as epilepsy, schizophrenia and Rett's syndrome, where pruning is thought to be defective. ..
  43. REGULATION OF INDUCIBLE NITRIC OXIDE SYNTHASE IN KIDNEY
    BRUCE KONE; Fiscal Year: 2002
    ....
  44. SPHINGOLIPID METABOLITE, SPHINGOSINE 1 PHOSPHATE
    Sarah Spiegel; Fiscal Year: 2002
    ..This proposal provides a new paradigm for dissecting the complex interplay between intra and extracellular actions of sphingosine-1-phosphate. ..
  45. Regulation of the Actin Cytoskeleton in Dendric Spines
    Peter Penzes; Fiscal Year: 2002
    ..serine/threonine phosphorylation, and generate initial information about the types of protein kinases involved. Together, these experiments will provide a basis for future studies of regulation of kalirin-7 and spine morphogenesis. ..
  46. REGULATION OF PHOSPHOLIPASE C
    T Harden; Fiscal Year: 2002
    ..Completion of the work described in this proposal should considerably extend knowledge of the identify, specificity, and mechanism of interaction of the component proteins of the receptor-regulated inositol lipid signalling pathway. ..
  47. Molecular Cloning of the Wilms tumor Gene from 7p15-21
    Khalid Sossey Alaoui; Fiscal Year: 2004
    ..Understanding the nature of the genetic events which allow these cells to escape their normal growth regulation may also provide an opportunity for therapeutic intervention. ..
  48. FASEB Summer Research Conference on Small G-Proteins
    Jeffrey Settleman; Fiscal Year: 2004
    ..The conference will cover the biochemical, structural, and functional aspects of the various small GTPases and their regulators and targets. ..
  49. Phagocyte Contact Response in Aspergillosis Immunity
    JAMES BURRITT; Fiscal Year: 2005
    ..fumigatus resting conidia, swollen conidia, and hyphae with a peptide library. This information will be used to suggest mechanisms of attachment in this host-pathogen relationship ..
  50. A Growth-Regulating Protein Tyrosine Phosphatase
    Jonathan Chernoff; Fiscal Year: 2007
    ..Importantly, it also may point the way to the development of new therapeutic agents for diseases such as diabetes and cancer. ..
  51. REGULATION OF SUPEROXIDE PRODUCTION BY HUMAN NEUTROPHILS
    Jeffrey Friedman; Fiscal Year: 2007
    ..These studies may ultimately lead to new pharmacological methods for controlling oxygen radical-mediated tissue damage as well as an improved understanding of the pathophysiology of CGD. ..
  52. 2006 NOX Family NADPH Oxidases Gordon Conference
    WILLIAM NAUSEEF; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  53. Regulated cytoskeletal dynamics in the secretory pathway
    Mark Stamnes; Fiscal Year: 2006
    ..abstract_text> ..
  54. VEGF-dependent and - Independent Anti-angiogenic Therapy
    Calvin Kuo; Fiscal Year: 2006
    ..Moreover, these humanized receptors will be expressed from regulated adenoviruses to confer an additional degree of safety as a prelude to eventual clinical use. ..
  55. G PROTEIN SUBUNITS--CELL BIOLOGY AND SIGNALING
    Henry Bourne; Fiscal Year: 2001
    ..4) Define interactions of the G-alpha with three proteins - actin, caveolin and members of the G-alpha-interacting protein (GAIP) family-that may inhibit G protein signaling by interacting with and sequestering G-alpha subunit. ..
  56. Regulation and Functin of the p190 RhoGAPs
    Jeffrey Settleman; Fiscal Year: 2006
    ..This is an important step toward establishing an accurate picture of the regulatory mechanisms for small GTPases in vivo, and the nature of their dysregulation in human cancers. ..
  57. REGULATION OF HUMAN PHAGOCYTE FUNCTION BY RAC PROTEINS
    Ulla Knaus; Fiscal Year: 2006
    ..These studies will yield novel insights into the overall control of oxidant formation by innate immune cells. ..
  58. CHAPERONES AND PROTEIN BIOSYNTHESIS IN MYELOID CELLS
    WILLIAM NAUSEEF; Fiscal Year: 2005
    ..The applicants believe that these will define principles that apply not only to these specific myeloid proteins but to proteins in general that acquire heme in the ER. ..
  59. Role of AML1/ETO in Hematopoiesis and Leukemogenesis
    JAMES MULLOY; Fiscal Year: 2005
    ..The establishment of a small animal model of AML will greatly enhance our ability to develop and test treatment strategies and drugs that may be useful in the therapy of AML. ..
  60. The Submembranous Cytoskeleton in Neutrophil Activation
    WILLIAM NAUSEEF; Fiscal Year: 2005
    ..Fundamental principles elucidated already have been applied to studies of specific host-pathogen interactions. ..
  61. The Role of MLL-AF9 in Acute Myeloid Leukemia
    James C Mulloy; Fiscal Year: 2010
    ..RELEVANCE (See instructions): We have recently shown that human blood stem cells can be induced to make leukemia upon introduction ..
  62. G protein signal integration by multifunctional proteins
    T Harden; Fiscal Year: 2006
    ..abstract_text> ..
  63. Molecular Mechanisms of MIG-10 function in axon guidance
    Christopher Quinn; Fiscal Year: 2005
    ..Information from this project will be beneficial in understanding disorders of the nervous system as well as the molecular basis of cancer. ..