cdc42 gtp binding protein

Summary

Summary: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.

Top Publications

  1. 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
  2. ncbi Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells
    Edgar R Gomes
    Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA
    Cell 121:451-63. 2005
  3. ncbi The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42
    G Joberty
    Markey Center for Cell Signaling, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908 0577, USA
    Nat Cell Biol 2:531-9. 2000
  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. pmc Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells
    Reina E Itoh
    Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, CREST, Japan
    Mol Cell Biol 22:6582-91. 2002
  6. pmc Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis
    Adam D Hoppe
    Department of Microbiology and Immunology and the Biophysics Research Division, University of Michigan Medical School, Ann Arbor, Michigan 48109 0620, USA
    Mol Biol Cell 15:3509-19. 2004
  7. pmc PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia
    A Abo
    Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA
    EMBO J 17:6527-40. 1998
  8. 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
  9. 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
  10. ncbi Par-3 controls tight junction assembly through the Rac exchange factor Tiam1
    Xinyu Chen
    Center for Cell Signaling, Department of Microbiology, HSC, University of Virginia, Charlottesville, Virginia 22908, USA
    Nat Cell Biol 7:262-9. 2005

Detail Information

Publications272 found, 100 shown here

  1. 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...
  2. ncbi Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells
    Edgar R Gomes
    Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA
    Cell 121:451-63. 2005
    ..These results show that nuclear repositioning is an initial polarizing event in migrating cells and that the positions of the nucleus and the MTOC are established by separate regulatory pathways...
  3. ncbi The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42
    G Joberty
    Markey Center for Cell Signaling, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908 0577, USA
    Nat Cell Biol 2:531-9. 2000
    ..This assembly is implicated in the formation of normal tight junctions at epithelial cell-cell contacts. Thus, Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3...
  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. pmc Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells
    Reina E Itoh
    Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, CREST, Japan
    Mol Cell Biol 22:6582-91. 2002
    ..In conclusion, use of these single-molecule probes to determine Rac and Cdc42 activity will accelerate the analysis of the spatiotemporal regulation of Rac and Cdc42 in a living cell...
  6. pmc Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis
    Adam D Hoppe
    Department of Microbiology and Immunology and the Biophysics Research Division, University of Michigan Medical School, Ann Arbor, Michigan 48109 0620, USA
    Mol Biol Cell 15:3509-19. 2004
    ..These distinct roles for Cdc42, Rac1, and Rac2 in the component activities of phagocytosis indicate mechanisms by which their differential regulation coordinates rearrangements of actin and membranes...
  7. pmc PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia
    A Abo
    Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA
    EMBO J 17:6527-40. 1998
    ..Thus, unlike other members of the PAK family, PAK4 provides a novel link between Cdc42Hs and the actin cytoskeleton. The cellular locations of PAK4 and Cdc42Hs suggest a role for the Golgi in cell morphogenesis...
  8. 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...
  9. 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...
  10. ncbi Par-3 controls tight junction assembly through the Rac exchange factor Tiam1
    Xinyu Chen
    Center for Cell Signaling, Department of Microbiology, HSC, University of Virginia, Charlottesville, Virginia 22908, USA
    Nat Cell Biol 7:262-9. 2005
    ..These results define a critical function for Par-3 in tight junction assembly, and reveal a novel mechanism through which Par-3 engages in the spatial regulation of Rac activity and establishment of epithelial polarity...
  11. ncbi Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization
    A F Palazzo
    Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA
    Curr Biol 11:1536-41. 2001
    ..MTOC reorientation and MT stabilization both act to polarize the MT array in migrating cells, yet these processes act independently and are regulated by separate Rho family GTPase-signaling pathways...
  12. 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...
  13. ncbi Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170
    Masaki Fukata
    Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466 8550, Japan
    Cell 109:873-85. 2002
    ..These results indicate that Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization...
  14. 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...
  15. pmc Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters
    G Fritz
    Institute of Toxicology, Division of Applied Toxicology, University of Mainz, Obere Zahlbacher Str 67, D 55131 Mainz, Germany
    Br J Cancer 87:635-44. 2002
    ....
  16. ncbi Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion
    Simon Wilkinson
    Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nat Cell Biol 7:255-61. 2005
    ..Our data show that a Cdc42-MRCK signal mediates myosin-dependent cell motility and highlight convergence between Rho and Cdc42 signalling...
  17. 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...
  18. 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...
  19. pmc Concentric zones of active RhoA and Cdc42 around single cell wounds
    Hélène A Benink
    Department of Zoology, University of Wisconsin Madison, Madison, WI 53706, USA
    J Cell Biol 168:429-39. 2005
    ..Each of the zones makes distinct contributions to the organization and function of the actomyosin wound array. We propose that similar rho activity zones control related processes such as cytokinesis...
  20. ncbi Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI
    G R Hoffman
    Department of Molecular Medicine, Veterinary Medical Center, Cornell University, Ithaca, New York 14853, USA
    Cell 100:345-56. 2000
    ..The structural data demonstrate how GDIs serve as negative regulators of small GTP-binding proteins and how the isoprenoid moiety is utilized in this critical regulatory interaction...
  21. 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...
  22. pmc PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42
    Fernando Martin-Belmonte
    Department of Anatomy, University of California, San Francisco, CA 94143, USA
    Cell 128:383-97. 2007
    ..Loss of function of PTEN, Anx2, Cdc42, or aPKC prevents normal development of the apical surface and lumen. We conclude that the mechanism of PTEN, PtdIns(4,5)P2, Anx2, Cdc42, and aPKC controls apical plasma membrane and lumen formation...
  23. pmc Actin pedestal formation by enteropathogenic Escherichia coli and intracellular motility of Shigella flexneri are abolished in N-WASP-defective cells
    S Lommel
    Institute for Genetics, University of Koln, Weyertal 121, 50931 Koln, Germany
    EMBO Rep 2:850-7. 2001
    ..Our results prove the essential role of this protein for actin cytoskeletal changes induced by these bacterial pathogens in vivo and in addition show for the first time that N-WASP is dispensable for filopodia formation...
  24. pmc Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis
    Aron B Jaffe
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Cell Biol 183:625-33. 2008
    ..We conclude that Cdc42 regulates epithelial tissue morphogenesis by controlling spindle orientation during cell division...
  25. ncbi Spatio-temporal regulation of Rac1 and Cdc42 activity during nerve growth factor-induced neurite outgrowth in PC12 cells
    Kazuhiro Aoki
    Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita Shi, Osaka 565 0871, Japan
    J Biol Chem 279:713-9. 2004
    ..It was concluded that the localized activation of Rac1 and Cdc42 was caused by both guanine nucleotide exchange factors and GAPs, and was important for neurite extension...
  26. ncbi Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP
    H Miki
    Department of Biochemistry, Institute of Medical Science, University of Tokyo, Japan
    Nature 391:93-6. 1998
    ..This activation seems to be caused by exposure of N-WASP's actin-depolymerizing region induced by Cdc42 binding...
  27. ncbi Rac/Cdc42 and p65PAK regulate the microtubule-destabilizing protein stathmin through phosphorylation at serine 16
    H Daub
    Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research Campaign Oncogene and Signal Transduction Group, and the Department of Biochemistry, University College London, Gower Street, London WC1E 6BT, United Kingdom
    J Biol Chem 276:1677-80. 2001
    ..Because stathmin destabilizes microtubules, and this process is inhibited by phosphorylation at residue 16, Rac and Cdc42 can potentially regulate both F-actin and microtubule dynamics...
  28. pmc Similar requirements for CDC-42 and the PAR-3/PAR-6/PKC-3 complex in diverse cell types
    David P Welchman
    The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, CB2 1QN, UK
    Dev Biol 305:347-57. 2007
    ..We also propose a novel role for primordial germ cells in mediating coalescence of the Caenorhabditis elegans gonad. These results indicate that CDC-42 and the PAR-3/PAR-6/aPKC complex function together in diverse cell types...
  29. ncbi Cdc42 interacts with the exocyst and regulates polarized secretion
    X Zhang
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Biol Chem 276:46745-50. 2001
    ..These results have revealed a role for Cdc42 in exocytosis. We propose that Cdc42 coordinates the vesicle docking machinery and the actin cytoskeleton for polarized secretion...
  30. ncbi Activation of type I phosphatidylinositol 4-phosphate 5-kinase isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42
    Paschal A Oude Weernink
    Institut fur Pharmakologie, Universitatsklinikum Essen, Essen 45122, Germany
    J Biol Chem 279:7840-9. 2004
    ....
  31. ncbi Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex
    K E Prehoda
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143 0450, USA
    Science 290:801-6. 2000
    ..This cooperative activation mechanism shows how combinations of simple binding domains can be used to integrate and amplify coincident signals...
  32. 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...
  33. pmc Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages
    S Linder
    Max von Pettenkofer Institut für Medizinische Mikrobiologie, Pettenkoferstrasse 9a, Ludwig Maximilians Universitat, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 96:9648-53. 1999
    ..These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages...
  34. pmc Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts
    Linda Yang
    Division of Experimental Hematology, Children s Hospital Medical Center, Molecular Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, OH 45229, USA
    Mol Biol Cell 17:4675-85. 2006
    ..These results demonstrate a different requirement of Cdc42 activity in primary MEFs from ES or ES-derived clonal fibroblastoid cells and suggest that Cdc42 plays cell-type-specific signaling roles...
  35. ncbi Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation
    Wen Jin Wu
    Department of Molecular Medicine, Veterinary Medical Center, Baker Laboratory, Cornell University, Ithaca, NY 14853, USA
    Cell 114:715-25. 2003
    ....
  36. ncbi EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP
    Fumitoshi Irie
    The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Neurosci 5:1117-8. 2002
  37. ncbi Regulation of PTEN by Rho small GTPases
    Zhong Li
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
    Nat Cell Biol 7:399-404. 2005
    ..Furthermore, we have identified key residues on PTEN that are required for its regulation by the small GTPase, and show that small GTPase-mediated regulation of PTEN has a significant role in the regulation of chemotaxis...
  38. ncbi Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product
    M J Hart
    Department of Biochemistry, Cornell University, Ithaca, New York 14853
    Nature 354:311-4. 1991
    ....
  39. ncbi Activation of phosphoinositide 3-kinase activity by Cdc42Hs binding to p85
    Y Zheng
    Department of Pharmacology, Cornell University, Ithaca, New York 14853
    J Biol Chem 269:18727-30. 1994
    ..These findings suggest that PI 3-kinase, through the Rho-GAP homology domain of p85, can couple to the effector domain of Cdc42Hs and that p85 may be a target for the GTP-bound forms of Cdc42Hs and Rac1...
  40. ncbi AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling
    Melanie L Yarbrough
    Department of Molecular Biology, University of Texas UT Southwestern Medical Center, Dallas, TX 75390, USA
    Science 323:269-72. 2009
    ..Eukaryotic proteins were also directly modified with AMP, potentially expanding the repertoire of posttranslational modifications for molecular signaling...
  41. ncbi Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure
    A Jacinto
    Department of Anatomy and Developmental Biology, University College London, Gower Street, WC1E 6BT, London, UK
    Curr Biol 10:1420-6. 2000
    ..Although many components of the signalling cascade directing this process have been identified, the precise cell-biological events upon which these signals act remain poorly described...
  42. ncbi Rho-family GTPases: it's not only Rac and Rho (and I like it)
    Krister Wennerberg
    Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    J Cell Sci 117:1301-12. 2004
    ..Newer members of the family possess additional sequence elements beyond the GTPase domain, which suggests they exhibit yet other mechanisms of regulation...
  43. ncbi IQGAP1 promotes cell motility and invasion
    Jennifer M Mataraza
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School Boston, Massachusetts 02115, USA
    J Biol Chem 278:41237-45. 2003
    ..Moreover, invasion mediated by constitutively active Cdc42 was attenuated by IQGAP1DeltaGRD. Thus, IQGAP1 has a fundamental role in cell motility and invasion...
  44. pmc Dynamics of ligand-induced, Rac1-dependent anchoring of cadherins to the actin cytoskeleton
    Mireille Lambert
    Signalisation et Différenciation Cellulaires dans les Systèmes Nerveux et Musculaire, INSERM U440, Universite Paris 6, Institut du Fer a Moulin, 75005 Paris, France
    J Cell Biol 157:469-79. 2002
    ....
  45. ncbi Association of Cdc42/N-WASP/Arp2/3 signaling pathway with Golgi membranes
    Olga B Matas
    Departament de Biologia Cellular i Anatomia Patologica, Facultat de Medicina, Universitat de Barcelona IDIBAPS, 08036 Barcelona, Spain
    Traffic 5:838-46. 2004
    ..These results show that the actin nucleation and polymerization signaling pathway governed by Cdc42/N-WASP/Arp operates in the Golgi complex of mammalian cells, further implicating actin dynamics in Golgi-associated membrane trafficking...
  46. pmc Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization
    T Leung
    Glaxo IMCB Group, Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge, Singapore
    Mol Cell Biol 18:130-40. 1998
    ..These results suggest that MRCK alpha may act as a downstream effector of Cdc42 in cytoskeletal reorganization...
  47. pmc Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2
    T Sumi
    Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan
    J Cell Biol 147:1519-32. 1999
    ....
  48. 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...
  49. ncbi Phosphorylation of the Cdc42 exchange factor Cdc24 by the PAK-like kinase Cla4 may regulate polarized growth in yeast
    M P Gulli
    Swiss Institute for Experimental Cancer Research Chemin des Boveresses 155 1066 Epalinges, Vaud, Switzerland
    Mol Cell 6:1155-67. 2000
    ....
  50. pmc Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin
    Xunwei Wu
    Max Planck Institute of Biochemistry, Heisenberg Group Regulation of Cytoskeletal Organization, Department of Molecular Medicine, 82152 Martinsried, Germany
    Genes Dev 20:571-85. 2006
    ..These data suggest that Cdc42 regulation of beta-catenin turnover is important for terminal differentiation of HF progenitor cells in vivo...
  51. ncbi A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42
    E Manser
    Institute of Molecular and Cell Biology, National University of Singapore
    Nature 363:364-7. 1993
    ..Our findings indicate that there may be a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation pathway...
  52. ncbi Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity
    Sandrine Etienne-Manneville
    MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, and Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK
    Nature 421:753-6. 2003
    ..We conclude that Cdc42 regulates cell polarity through the spatial regulation of GSK-3beta and Apc. This role for Apc may contribute to its tumour-suppressor activity...
  53. pmc Regulation of protein transport from the Golgi complex to the endoplasmic reticulum by CDC42 and N-WASP
    Ana Luna
    Departament de Biologia Cel lular i Anatomia Patològica, Facultat de Medicina, Institut d Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, E 08036 Barcelona, Spain
    Mol Biol Cell 13:866-79. 2002
    ..Furthermore, Cdc42V12 recruited GFP-N-WASP to the Golgi complex. We therefore conclude that Cdc42 regulates Golgi-to-ER protein transport in an N-WASP-dependent manner...
  54. 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...
  55. ncbi Asymmetric positioning and organization of the meiotic spindle of mouse oocytes requires CDC42 function
    Jie Na
    The Wellcome Trust Cancer Research UK Gurdon Institute of Cancer and Developmental Biology and Department of Genetics, University of Cambridge, Cambridge CB2 1QR, United Kingdom
    Curr Biol 16:1249-54. 2006
    ..Thus, at least two pathways appear to be downstream of CDC42: one affecting the actin cytoskeleton and required for migration of the meiotic spindle, and a second affecting the spindle microtubules in which aPKCzeta plays a role...
  56. ncbi Involvement of Cdc42 and Rac small G proteins in invadopodia formation of RPMI7951 cells
    Hirokazu Nakahara
    The First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Suita 565 0871, Japan
    Genes Cells 8:1019-27. 2003
    ..We studied the roles of the Rho family small G proteins in invadopodia formation...
  57. ncbi Localized cdc42 activation, detected using a novel assay, mediates microtubule organizing center positioning in endothelial cells in response to fluid shear stress
    Eleni Tzima
    Department of Cell Biology, Division of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:31020-3. 2003
    ..Thus, shear-stimulated integrin dynamics induce polarized Cdc42 activity, which induces MTOC localization through the Par6-protein kinase Czeta complex...
  58. ncbi The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis
    N Gnesutta
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 276:14414-9. 2001
    ..Consistent with an antiapoptotic function, expression of PAK4 leads to an increase in phosphorylation of the proapoptotic protein Bad and an inhibition of caspase activation...
  59. pmc Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis
    T Tatsumoto
    Molecular Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    J Cell Biol 147:921-8. 1999
    ..These results suggest that ECT2 is an important link between the cell cycle machinery and Rho signaling pathways involved in the regulation of cell division...
  60. ncbi Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration
    Takashi Watanabe
    Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466 8550, Japan
    Dev Cell 7:871-83. 2004
    ....
  61. ncbi Recruitment of Dbl by ezrin and dystroglycan drives membrane proximal Cdc42 activation and filopodia formation
    Clare L Batchelor
    Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, UK
    Cell Cycle 6:353-63. 2007
    ..Depletion of dystroglycan inhibited Cdc42-induced filopodia formation. For the first time we also demonstrate co-localization of Cdc42 and dystroglycan at the tips of dynamic filopodia...
  62. pmc Intersectin-1L nucleotide exchange factor regulates secretory granule exocytosis by activating Cdc42
    Magali Malacombe
    Département Neurotransmission and Sécrétion Neuroendocrine, Institut des Neurosciences Cellulaires et Intégratives UMR 7168 LC2, Centre National de la Recherche Scientifique and Université Louis Pasteur, Strasbourg, France
    EMBO J 25:3494-503. 2006
    ..Our results extend the current role of intersectin-1L in endocytosis to a function in exocytosis and support the idea that intersectin-1L is an adaptor that coordinates exo-endocytotic membrane trafficking in secretory cells...
  63. pmc Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2
    Takashi Nishimura
    Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466 8550, Japan
    Mol Biol Cell 17:1273-85. 2006
    ..Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation. These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2...
  64. 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...
  65. ncbi Borg proteins control septin organization and are negatively regulated by Cdc42
    G Joberty
    Markey Center for Cell Signaling and Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA
    Nat Cell Biol 3:861-6. 2001
    ..Cdc42 negatively regulates this effect and inhibits the binding of Borg3 to septins. Borgs are therefore the first known regulators of mammalian septin organization and provide an unexpected link between the septin and Cdc42 GTPases...
  66. 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
    ....
  67. ncbi Cellular signaling for activation of Rho GTPase Cdc42
    Soniya Sinha
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
    Cell Signal 20:1927-34. 2008
    ..This review will discuss the molecular mechanism of activation of Cdc42 and postulate that signaling specificity of Cdc42 is conferred by the GEF/GTPase/Effector (GGE) complexes in response to external stimuli...
  68. 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...
  69. 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
    ....
  70. pmc Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing the 58-kD insulin receptor substrate to filamentous actin
    S Govind
    Department of Neurochemistry, Institute of Neurology, London WC1N 1PJ, United Kingdom
    J Cell Biol 152:579-94. 2001
    ..These results suggest that Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing protein complexes via adaptor proteins such as IRS-58 to F-actin...
  71. ncbi Rho-kinase phosphorylates PAR-3 and disrupts PAR complex formation
    Masanori Nakayama
    Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa Ku, Nagoya, Aichi 466 8550, Japan
    Dev Cell 14:205-15. 2008
    ..We propose that RhoA/Rho-kinase inhibits PAR complex formation through PAR-3 phosphorylation, resulting in Rac1 inactivation...
  72. 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
    ....
  73. 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...
  74. ncbi GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway
    Shefali Sabharanjak
    National Centre for Biological Sciences, UAS GKVK Campus, Bellary Road, 560 065, Bangalore, India
    Dev Cell 2:411-23. 2002
    ..These results describe a distinct constitutive pinocytic pathway, specifically regulated by cdc42...
  75. ncbi Potential roles of the nucleotide exchange factor ECT2 and Cdc42 GTPase in spindle assembly in Xenopus egg cell-free extracts
    Takashi Tatsumoto
    Molecular Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Cell Biochem 90:892-900. 2003
    ..These results suggest that the Rho family GTPase Cdc42 and its exchange factor XECT2 are critical regulators of spindle assembly in Xenopus egg extracts...
  76. pmc Activity of Rho-family GTPases during cell division as visualized with FRET-based probes
    Hisayoshi Yoshizaki
    Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Japan
    J Cell Biol 162:223-32. 2003
    ..In conclusion, we could use the FRET-based probes to visualize the complex spatio-temporal regulation of Rho-family GTPases during cell division...
  77. pmc Paxillin-dependent paxillin kinase linker and p21-activated kinase localization to focal adhesions involves a multistep activation pathway
    Michael C Brown
    Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse 13210, USA
    Mol Biol Cell 13:1550-65. 2002
    ..This mechanism is probably critical for the correct subcellular positioning of PAK, thereby influencing the ability of PAK to coordinate cytoskeletal reorganization associated with changes in cell shape and motility...
  78. pmc Vav2 activates Rac1, Cdc42, and RhoA downstream from growth factor receptors but not beta1 integrins
    B P Liu
    Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7090, USA
    Mol Cell Biol 20:7160-9. 2000
    ..Expression of a carboxy-terminal fragment of Vav2 decreased the elevation of Rac1 activity induced by epidermal growth factor, consistent with Vav2 mediating activation of Rac1 downstream from growth factor receptors...
  79. ncbi Regulation of Rho family GTPases by cell-cell and cell-matrix adhesion
    William T Arthur
    Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Biol Res 35:239-46. 2002
    ....
  80. ncbi Probing single-molecule protein conformational dynamics
    H Peter Lu
    Pacific Northwest National Laboratory, Fundamental Science Division, P O Box 999, Richland, Washington 99352, USA
    Acc Chem Res 38:557-65. 2005
    ..Alternatively, single-molecule spectroscopy is a powerful approach to probing and analyzing protein conformational dynamics in real time...
  81. pmc Gene 33/Mig-6, a transcriptionally inducible adapter protein that binds GTP-Cdc42 and activates SAPK/JNK. A potential marker transcript for chronic pathologic conditions, such as diabetic nephropathy. Possible role in the response to persistent stress
    A Makkinje
    Diabetes Unit, Medical Services, Massachusetts General Hospital and the Department of Medicine, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 275:17838-47. 2000
    ..Expression of Gene 33 at sufficient levels may enable a compensatory reprogramming of cellular function in response to chronic stress, which may have pathophysiological consequences...
  82. ncbi Two actions of frabin: direct activation of Cdc42 and indirect activation of Rac
    Y Ono
    Takai Biotimer Project, ERATO, Japan Science and Technology Corporation, c o JCR Pharmaceuticals Co Ltd, 2 2 10 Murotani, Nishi ku, Kobe 651 2241, Japan
    Oncogene 19:3050-8. 2000
    ..The FYVE domain and the second PH domain in addition to the DH domain and the first PH domain are necessary for the lamellipodium-like structure formation. We show here these two actions of frabin in the regulation of cell morphology...
  83. ncbi The Cdc42 and Rac1 GTPases are required for capillary lumen formation in three-dimensional extracellular matrices
    Kayla J Bayless
    Department of Pathology and Laboratory Medicine, Texas A and M University System Health Science Center, College Station, Texas 77843 1114, USA
    J Cell Sci 115:1123-36. 2002
    ..These results collectively reveal a novel role for Cdc42 and Rac1 in the process of EC vacuole and lumen formation in three-dimensional extracellular matrices...
  84. ncbi Evolutionary expansion of CRIB-containing Cdc42 effector proteins
    D M Pirone
    Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
    Trends Genet 17:370-3. 2001
    ..These evolutionary changes correlate with the development of the more complex signaling pathways present in higher organisms...
  85. ncbi Regulation of neuronal morphology by Toca-1, an F-BAR/EFC protein that induces plasma membrane invagination
    Tetsuhiro Kakimoto
    Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 281:29042-53. 2006
    ..These results suggest that a vesicle trafficking regulator Toca-1 regulates different aspects of neuronal morphology from N-WASP...
  86. ncbi Regulation of cell polarity and protrusion formation by targeting RhoA for degradation
    Hong Rui Wang
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M56 1x5, Canada
    Science 302:1775-9. 2003
    ..Smurf1 thus links the polarity complex to degradation of RhoA in lamellipodia and filopodia to prevent RhoA signaling during dynamic membrane movements...
  87. ncbi S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells
    W D Hardt
    Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, 11794 5222, USA
    Cell 93:815-26. 1998
    ..These findings establish a paradigm for microbial stimulation of cellular responses in which the pathogen induces signaling events by directly engaging the signaling machinery within the host cell...
  88. pmc The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin signaling
    Kathleen Szczur
    Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation, and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Blood 114:4527-37. 2009
    ..Our results uncover a new mechanism in which Cdc42 regulates the uropod through CD11b signaling to maintain polarity in migrating neutrophils. It also reveals new functions for CD11b in neutrophil polarity...
  89. ncbi Multiple roles for Cdc42 in cell regulation
    J W Erickson
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853, USA
    Curr Opin Cell Biol 13:153-7. 2001
    ..g. WASP) and cellular stress pathways (e.g. PAK) and with regard to newly identified targets such as the coatomer protein complex and PAR6. Recent results hint at a previously unappreciated link between these various cellular processes...
  90. pmc A novel role of nectins in inhibition of the E-cadherin-induced activation of Rac and formation of cell-cell adherens junctions
    Takashi Hoshino
    Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine Faculty of Medicine, Suita 565 0871, Japan
    Mol Biol Cell 15:1077-88. 2004
    ..These results indicate a novel role of nectins in regulation of the E-cadherin-induced activation of Rac and formation of cell-cell AJs...
  91. ncbi Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization
    M Symons
    Onyx Pharmaceuticals, Richmond, California 94806, USA
    Cell 84:723-34. 1996
    ..The WASP sequence contains two novel domains that are homologous to other proteins involved in action organization...
  92. ncbi Fibroblast growth factor 2 endocytosis in endothelial cells proceed via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway
    Eugene Tkachenko
    Angiogenesis Research Center, Department of Medicine, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
    J Cell Sci 117:3189-99. 2004
    ..Taken together, these results demonstrate that FGF2 endocytosis requires syndecan-4 clustering-dependent activation of Rac1 and the intact CDC42-dependent macropinocytic pathway...
  93. pmc Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration
    Brian Stramer
    Department of Physiology, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK
    J Cell Biol 168:567-73. 2005
    ..Cdc42 is necessary for maintaining cellular polarity and yet, despite in vitro evidence, is dispensable for sensing and crawling toward wound cues...
  94. pmc Rho GTPase Cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow
    Linda Yang
    Division of Experimental Hematology and Pathology, Cincinnati Children s Research Foundation, Molecular Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 104:5091-6. 2007
    ..Thus, Cdc42 is a critical coordinator of HSC quiescence maintenance and interaction with the BM niche...
  95. ncbi Trans-interactions of nectins induce formation of filopodia and Lamellipodia through the respective activation of Cdc42 and Rac small G proteins
    Tomomi Kawakatsu
    Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine Faculty of Medicine, Suita 565 0871, Japan
    J Biol Chem 277:50749-55. 2002
    ..These effects of nectins require their cytoplasmic tail but not their association with afadin. We propose here the functional relationship between nectins and the small G proteins in the organization of AJs...
  96. ncbi Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein
    A S Kim
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 404:151-8. 2000
    ..These data show that 'intrinsically unstructured' peptides such as the GTPase-binding domain of WASP can be induced into distinct structural and functional states depending on context...
  97. ncbi Distribution of the small molecular weight GTP-binding proteins Rac1, Cdc42, RhoA and RhoB in the developing chick retina
    Andréa Silveira Santos-Bredariol
    Department of Histology and Embryology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05508 900, Brazil
    J Neurocytol 31:149-59. 2002
    ..The distribution pattern of Rho proteins during the development of the chick retina suggests a concerted role in the differentiation of specific cell types, and probably during synaptogenesis...
  98. ncbi Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration
    Naël Osmani
    Cell Polarity and Migration Group, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    Curr Biol 16:2395-405. 2006
    ..Cdc42 is, in particular, required for polarization and orientation of astrocytes in a scratch-induced polarized migration assay. Using this assay, we characterized Scrib function during polarized cell migration...
  99. ncbi Cdc42 is required for PIP(2)-induced actin polymerization and early development but not for cell viability
    F Chen
    Departments of Genetics, The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 10:758-65. 2000
    ..Also, whereas genetic analyses have shown that Cdc42 is essential for cell viability in yeast, its potential roles in the growth and development of mammalian cells have not been directly assessed...
  100. ncbi Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms
    Victor May
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05404, USA
    J Neurosci 22:6980-90. 2002
    ..Thus Kalirin, acting via RhoG in a novel manner, plays a central role in establishing the morphological phenotypic diversity that is essential to the connectivity of the developing nervous system...
  101. ncbi The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity
    Jens C Schwamborn
    Abteilung Molekularbiologie, Institut fur Allgemeine Zoologie und Genetik, Westfalische Wilhelms Universitat Munster, Germany
    Nat Neurosci 7:923-9. 2004
    ..Using GTPase mutants and RNA interference, we found that Rap1B is necessary and sufficient to initiate the development of axons upstream of Cdc42 and the Par complex...

Research Grants64

  1. RAS/CDC42 DEPENDENT SIGNAL TRANSDUCTION IN FISSION YEAST
    Stevan Marcus; Fiscal Year: 2000
    ..Our long-term objective is to apply the knowledge obtained from our studies on Ras1/Cdc42/shk1-dependent signal transduction in fission yeast toward gaining an understanding of related signaling pathways in higher organisms. ..
  2. CONTROL OF PHAGOCYTE NADPH OXIDASE BY CYTOSOLIC PROTEINS
    Gary Bokoch; Fiscal Year: 2005
    ....
  3. ROLE OF PROTEIN PHOSPHATASES IN INSULIN SECRETION
    Anjaneyulu Kowluru; Fiscal Year: 2004
    ....
  4. Rho-Dependent COX-2 Expression in Intestinal Cells
    Lee Slice; Fiscal Year: 2007
    ..3) Define the role of Rho and of Protein Kinases acting upstream and downstream of Rho in COX-2 expression in intestinal epithelial cells. 4) Characterize COX-2 promoter elements that are responsive to Rho. ..
  5. GTPase Activating Proteins in Aging and Osteoarthritis
    Lisa Fortier; Fiscal Year: 2007
    ..We anticipate that these findings will facilitate identification of target molecules for development of therapeutics modalities for OA. [unreadable] [unreadable] [unreadable]..
  6. Protein Prenyltransferases in Glucose-Stimulated Insulin Secretion
    Anjaneyulu Kowluru; Fiscal Year: 2010
    ....
  7. 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]..
  8. 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. ..
  9. 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. ..
  10. Polarity and Epithelial Cell-Pathogen Interactions
    Michael Hobert; Fiscal Year: 2006
    ..This proposal will also examine the role of the Rho GTPases on the transepithelial migration of neutrophils. ..
  11. Gene Expression Changes in Early 3D Renal Tubulogenesis
    JOSHUA LIPSCHUTZ; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  12. DEVELOPMENTAL CELL BIOLOGY OF DENDRITIC CELLS
    Ira Mellman; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  13. 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. ..
  14. Cytoskeletal Regulation of Outer Hair Cell Motility
    Federico Kalinec; Fiscal Year: 2007
    ..abstract_text> ..
  15. The Role of Annexin 2 in Mucosal Wound Healing
    Brian Babbin; Fiscal Year: 2007
    ..The candidates long term goal is to develop an academic career as a physician/scientist. [unreadable] [unreadable]..
  16. 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]..
  17. 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]..
  18. Wnt Proteins During Intestinal Repair and Regeneration
    Calvin Kuo; Fiscal Year: 2009
    ....
  19. 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. ..
  20. The Exocyst in Synthesis, Cystogenesis and Tubulogenesis
    JOSHUA LIPSCHUTZ; Fiscal Year: 2009
    ..abstract_text> ..
  21. TRE17 links actin remodeling & vesicle trafficking
    Margaret Chou; Fiscal Year: 2009
    ..Through this work we hope to understand how these functions are coordinated during cell movement, and to elucidate the mechanism of TRE17 transformation. ..
  22. 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. ..
  23. Signaling by p21-activated protein kinases
    JONATHAN D CHERNOFF; Fiscal Year: 2010
    ....
  24. BIOSYNTHESIS OF MEMBRANE PROTEIN GLYCOLIPID ANCHORS
    Anant K Menon; Fiscal Year: 2010
    ....
  25. CD44/VARIANT CYTOSKELETON IN BREAST CANCER PROGRESSION
    LILLY YW BOURGUIGNON; Fiscal Year: 2010
    ....
  26. VEGF Regulation of Hepatic Erythropoietin Synthesis
    Calvin Kuo; Fiscal Year: 2009
    ....
  27. Mechanotransduction in Fibroblast
    Diane L Barber; Fiscal Year: 2010
    ....
  28. 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. ..
  29. Regulation of Cell Migration by the APC-Microtubule Complex
    William Nelson; Fiscal Year: 2009
    ..abstract_text> ..
  30. Allosteric, Small-Molecule Inhibitors of Actin Nucleation by the Formin mDia1
    Jeffrey Peterson; Fiscal Year: 2008
    ..Future work will apply this screen to a much larger compound collection and we envisage applying a similar strategy to develop inhibitors for other formins. [unreadable] [unreadable] [unreadable]..
  31. Olympus FV1000 Laser Scanning Confocal Microscope
    William Bement; Fiscal Year: 2007
    ..This information, in turn, will help guide future investigations of a number of normal and pathological human processes such as wound repair, nerve regeneration, cancer, and birth defects. [unreadable] [unreadable] [unreadable]..
  32. 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. ..
  33. ONCOGENESIS/CONTROL--PHOSPHOINOSITIDE CYCLE/KINASE C
    Ian Macara; Fiscal Year: 2001
    ..Overall these studies should lead to significant new insights into signaling through the Ras pathway, and may lead to new therapeutic targets for certain types of cancer. ..
  34. NUCLEAR TRANSPORT IN SILICO-A VIRTUAL CELL APPROACH
    Ian Macara; Fiscal Year: 2005
    ..The proposal offers a unique opportunity to employ the combined expertise of cell biologists, yeast geneticists, computer scientists, physicists and mathematicians to raise our understanding of nuclear transport. ..
  35. Cytoskeleton Coordination in Neuronal Morphogenesis
    W Nelson; Fiscal Year: 2005
    ....
  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. Cytoskeletal Regulation of Outer Hair Cell Motility
    Federico Kalinec; Fiscal Year: 2004
    ..abstract_text> ..
  38. The Urokinase-CD87 System in Macrophage Activation
    Robert Sitrin; Fiscal Year: 2004
    ....
  39. Cell Biology of the Immune Response
    Ira Mellman; Fiscal Year: 2003
    ..4) To explore how the cellular basis of the immune response contributes to the pathogenecity of and potential immunological therapy for cancer and infectious disease. ..
  40. RECOMBINANT PROTEIN EXPRESSION FACILITY
    RICHARD CERIONE; Fiscal Year: 2005
    ..abstract_text> ..
  41. PKN1 KINASE AND TSG101 TUMOR SUPPRESSOR
    Peter Burbelo; Fiscal Year: 2002
    ..Together these studies may yield a mechanistic understanding of both the normal function of TSG101 and PKN1 and their role in cellular transformation and invasion. ..
  42. SIGNALING MECHANISMS OF SOMATOSTATIN RECEPTORS
    DIANE BARBER; Fiscal Year: 2002
    ....
  43. ConFocal Microscope For Real Time Cell Dynamics
    Ian Macara; Fiscal Year: 2002
    ..This instrument will significantly enhance the research mission of the School of Medicine. ..
  44. SYNAPSE STRUCTURE AND DEVELOPMENT
    W Nelson; Fiscal Year: 2001
    ..This research will aid in the prevention of psychiatric illness and the development of therapies for afflicted individuals. ..
  45. 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. ..
  46. Rho GtPase and Cell Cycle Regulation in Breast Cancer
    Catherine Welsh; Fiscal Year: 2005
    ..Welsh's progression to the status of independent investigator. ..
  47. JOEL MODEL JEM-1230 TRANSMISSION ELECTRON MICROSCOPE
    Ian Macara; Fiscal Year: 2005
    ..There will be 5 NIH-funded primary users, and at least 4 minor users. Instrument time will be reserved by users on a Web-based calendar. The hourly fee and scheduling will be determined by the advisory committee and PI. ..
  48. MOLECULAR SORTING DURING INTRACELLULAR TRANSPORT
    Ira Mellman; Fiscal Year: 2006
    ..5) To identify and characterize novel molecules that function during polarized sorting. Cell biological approaches will be applied together with mutant screens and expression analysis in Drosophila. ..
  49. Regulated cytoskeletal dynamics in the secretory pathway
    Mark Stamnes; Fiscal Year: 2006
    ..abstract_text> ..
  50. BIOCHEMICAL CHARACTERIZATION OF SIGNAL TRANSDUCTION
    RICHARD CERIONE; Fiscal Year: 2006
    ....
  51. Wangiella: a model for dematiaceous fungal pathogens
    PAUL SZANISZLO; Fiscal Year: 2007
    ..abstract_text> ..
  52. MOLECULAR BASIS OF RECEPTOR CYCLASE COUPLING
    Henry Bourne; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  53. 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. ..
  54. Mammalian Septin GTP-Binding Proteins
    Ian Macara; Fiscal Year: 2005
    ..3. It will be determined whether septin filaments are dynamic or stable in intact cells, and how they assemble and disassemble, using septin-GFP fusions, time-lapse fluorescence microscopy and photobleaching. ..
  55. SYNAPTOPODIN: BIOGENESIS & PLASTICITY OF SPINE APPARATUS
    Peter Mundel; Fiscal Year: 2008
    ..This should in the long-term enable us to develop novel therapies that tackle learning deficiencies and memory loss by modulating the expression of synaptopodin thereby promoting the cellular plasticity of the dendritic spine apparatus. ..
  56. Phospholipid flip-flop in biogenic membranes
    ANANT MENON; Fiscal Year: 2002
    ..We expect that our analyses will not only impact current understanding of membrane biogenesis, but also contribute to an understanding of glycolipid flip-flop events that are essential in the assembly of cell surface components. ..
  57. Function of CMG-2, an Anthrax Toxin Receptor
    George Davis; Fiscal Year: 2005
    ..Specific Aim #2. To identify CMG-2 co-receptors, such as integrins, which are involved in its ability to regulate protective antigen binding, proteolytic processing and internalization. ..
  58. Fox proteins mediate insulin-increasedPAI-1 transcription
    FREDERICK STANLEY; Fiscal Year: 2006
    ..This proposal sets forth a strategy for accomplishing these goals. [unreadable] [unreadable]..
  59. Genetic Reg. of Hematopoietic Stem Cell Mobilization
    Hartmut Geiger; Fiscal Year: 2007
    ..g. to muscle tissue, or to other hematopoietic niches. ..
  60. Angiopoietin-2 and Glioma Invasion
    Shi Yuan Cheng; Fiscal Year: 2008
    ..These studies could establish Ang2 and its effectors as potential therapeutic targets leading to the development of new anti-invasion strategies for glioma treatments. ..
  61. CD44-P185HER2 INTERACTION IN OVARIAN CANCER PROGRESSION
    LILLY BOURGUIGNON; Fiscal Year: 2007
    ..abstract_text> ..
  62. MICROVASCULAR REGULATION BY CRYPTIC ECM SIGNALS
    George Davis; Fiscal Year: 2002
    ..These signals may play an important role during tissue injury by influencing microvascular cellular responses such as arteriolar vasoactivity, leukocyte diapedesis, vascular cell proliferation and endothelial cell invasion. ..
  63. Intestinal Mucosal Wound Resealing by Restitution
    Brian Babbin; Fiscal Year: 2005
    ..Such studies will provide important insights into the molecular mechanisms of restitution which will provide a basis for therapeutics aimed at promoting wound closure. ..