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Regulation of Cytoskeletons and Cell Adhesions by the Rho Family GTPases.

Research Project

Project/Area Number 11480211
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionNagoya University (2000)
Nara Institute of Science and Technology (1999)

Principal Investigator

KAIBUCHI Kozo  School of Medicine, Nagoya University, Professor, 医学部, 教授 (00169377)

Co-Investigator(Kenkyū-buntansha) AMANO Mutsuki  Nara institute of Science and Technology, Biological Sciences, Research Associate, バイオサイエンス研究科, 助手 (90304170)
稲垣 直之  奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教授 (20223216)
門田 裕志  奈良先端科学技術大学院大学, バイオサイエンス研究科, 助手 (10294282)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2000: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1999: ¥9,100,000 (Direct Cost: ¥9,100,000)
KeywordsSmall GTPases / Rho-kinase / IQGAP1 / cadherin / cell migration / cell adhesion / Phosphorylation / CRMP-2 / Rho-kinase / IQGAP / 細胞質分裂
Research Abstract

The Rho family GTPases (Rho, Rac, and Cdc42) regulate cytoskeletons and cell adhesions through their specific effectors. However, the molecular mechanisms by which the Rho family GTPases regulate these cellular functions have been unknown. Recently, we found that Rho-kinase, an effector of Rho, regulates actin cytoskeleton by regulating the phosphorylation state of myosin light chain (MLC) and that IQGAP1, an effector of Rac and Cdc42, regulates cadherin-mediated cell-cell adhesion. The aim of the present study is to further clarify the mechanism how Rho family GTPases and their effectors regulate cytoskeletons and cell adhesions. Here we found several novel substrates of Rho-kinase : CRMP-2, adducin, MAP2, tau, calponin and EF-1α. CRMP-2 phosphorylation by Rho-kinase was involved in LPA-induced growth cone collapse. We also found that adducin phosphorylation by Rho-kinase modulated cell migration. The analysis of the physiological functions of their phosphorylations is on going. In addition, we demonstrated that the Cdc42/Rac/IQGAP1 system was involved in cell-cell dissociation during cell scattering through α-catenin relocalization. The results obtained here lead us to better understanding how Rho family GTPases regulate cytoskeletons and cell

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (74 results)

All Other

All Publications (74 results)

  • [Publications] N.Arimura: "Phosphorylation of collapsin response mediator protein-2 by Rho-kinase, Evidence for two separate signaling pathways for growth cone collapse"J.Biol.Chem.. 275. 23973-23980 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Nakamura: "Phosphorylation of ERM proteins at filopodia induced by Cdc42"Genes Cells. 5. 571-581 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Amano: "Regulation and functions of rho-associated kinase"Exp.Cell Res.. 261. 44-51 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Amano: "Purification and in vitro activity of Rho-associated kinase"Methods Enzymol.. 325. 149-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kaneko: "Identification of calponin as a novel substrate of Rho-kinase "Biochem. Biophys. Res. Commun.. 273. 110-116 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Kawajiri: "Identification of a novel beta-catenin-interacting protein"Biochem. Biophys. Res. Commun.. 273. 712-717 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Izawa: "Elongation factor-lalpha is a novel substrate of rho-associated kinase"Biochem. Biophys. Res. Commun.. 278. 72-78 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] I.Royal: "Activation of cdc42, rac, PAK, and rho-kinase in response to hepatocyte growth factor differentially regulates epithelial cell colony spreading and dissociation"Mol.Biol.Cell. 11. 1709-1725 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Inagaki: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II within post-synaptic dendritic spines of cultured hippocampal neurons"J.Biol.Chem.. 275. 27165-27171 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Sone: "Synaptic development is controlled in the periactive zones of drosophila synapses"Development. 127. 4157-4168 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kandabashi: "Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-lbeta"Circulation. 101. 1319-1323 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Miyamoto: "Changes in E-cadherin associated with cytoplasmic molecules in well and poorly differentiated endometrial cancer"Br.J.Cancer. 83. 1168-1175 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Ihara: "Crystallization and preliminary crystallographic analysis of the rho-binding domain of bovine rho-kinase"Acta. Crystallogr. D.Biol. Crystallogr.. 56. 1042-1044 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] P.A.Oude Weernink: "Stimulation of phosphatidylinositol-4-phosphate 5-kinase by Rho-kinase"J.Biol.Chem.. 275. 10168-10174 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Szaszi: "RhoA and rho kinase regulate the epithelial Na^+/H^+ exchanger NHE3. Role of myosin light chain phosphorylation"J.Biol.Chem.. 275. 28599-28606 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Hashimoto: "Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation"J.Neurochem.. 75. 373-382 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kanai-Azuma: "Co-localization of FAM and AF-6, the mammalian homologues of Drosophila faf and canoe, in mouse eye development"Mech.Dev.. 91. 383-386 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Hamaguchi: "Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N"Biochem. Biophys. Res. Commun.. 274. 825-830 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Fukata: "Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells"TRENDS in Pharm. Sci.. 22. 32-39 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Fukata: "Involvement of IQGAP1, an Effector of Rac1 and Cdc42 GTPases, in Cell-Cell Dissociation during Cell Scattering"Mol. Cell. Biol.. 21(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Arimura: "Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse"J.Biol.Chem.. 275. 23973-23980 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Nakamura: "Phosphorylation of ERM proteins at filopodia induced by Cdc42"Genes Cells. 5. 571-581 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Amano: "Regulation and functions of rho-associated kinase"Exp.Cell Res.. 261. 44-51 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Amano: "Purification and in vitro activity of Rho-associated kinase"Methods Enzymol.. 325. 149-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kaneko: "Identification of calponin as a novel substrate of Rho-kinase"Biochem.Biophys.Res.Commun.. 273. 110-116 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Kawajiri: "Identification of a novel beta-catenin-interacting protein"Biochem.Biophys.Res.Commun.. 273. 712-717 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Izawa: "Elongation factor-1alpha is a novel substrate of rho-associated kinase"Biochem.Biophys.Res.Commun.. 278. 72-78 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] I.Royal: "Activation of cdc42, rac, PAK, and rho-kinase in response to hepatocyte growth factor differentially regulates epithelial cell colony spreading and dissociation"Mol.Biol.Cell. 11. 1709-1725 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Inagaki: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II within post-synaptic dendritic spines of cultured hippocampal neurons"J.Biol.Chem.. 275. 27165-27171 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Sone: "Synaptic development is controlled in the periactive zones of drosophila synapses"Development. 127. 4157-4168 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kandabashi: "Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta"Circulation. 101. 1319-1323 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Miyamoto: "Changes in E-cadherin associated with cytoplasmic molecules in well and poorly differentiated endometrial cancer"Br.J.Cancer. 83. 1168-1175 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Ihara: "Crystallization and preliminary crystallographic analysis of the rho-binding domain of bovine rho-kinase"Acta.Crystallogr.D.Biol.Crystallogr.. 56. 1042-1044 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] P.A.Oude Weernink: "Stimulation of phosphatidylinositol-4-phosphate 5-kinase by Rho-kinase"J.Biol.Chem.. 275. 10168-10174 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Szaszi: "RhoA and rho kinase regulate the epithelial Na^+/H^+ exchanger NHE3. Role of myosin light chain phosphorylation"J.Biol.Chem.. 275. 28599-28606 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Hashimoto: "Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation"J.Neurochem.. 75. 373-382 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kanai-Azuma: "Co-localization of FAM and AF-6, the mammalian homologues of Drosophila faf and canoe, in mouse eye development"Mech.Dev.. 91. 383-386 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Hamaguchi: "Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N"Biochem.Biophys.Res.Commun.. 274. 825-830 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Fukata: "Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells"TRENDS in Pharm.Sci.. 22. 32-39 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Fukata: "Involvement of IQGAP1, an Effector of Rac1 and Cdc42 GTPases, in Cell-Cell Dissociation during Cell Scattering"Mol.Cell.Biol.. 21 (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Arimura: "Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse"J.Biol.Chem.. 275. 23973-23980 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Nakamura: "Phosphorylation of ERM proteins at filopodia induced by Cdc42"Genes Cells. 5. 571-581 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Amano: "Regulation and functions of rho-associated kinase"Exp.Cell Res.. 261. 44-51 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Amano: "Purification and in vitro activity of Rho-associated kinase"Methods Enzymol.. 325. 149-155 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Kaneko: "Identification of calponin as a novel substrate of Rho-kinase"Biochem. Biophys. Res.Commun.. 273. 110-116 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Kawajiri: "Identification of a novel beta-catenin-interacting protein"Biochem. Biophys. Res.Commun.. 273. 712-717 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Izawa: "Elongation factor-lalpha is a novel substrate of rho-associated kinase"Biochem. Biophys. Res.Commun.. 278. 72-78 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] I.Royal: "Activation of cdc42,rac, PAK, and rho-kinase in response to hepatocyte growth factor differentially regulates epithelial cell colony spreading and dissociation"Mol.Biol.Cell. 11. 1709-1725 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Inagaki: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II within post-synaptic dendritic spines of cultured hippocampal neurons"J.Biol.Chem.. 275. 27165-27171 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Sone: "Synaptic development is controlled in the periactive zones of drosophila synapses"Development.. 127. 4157-4168 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Kandabashi: "Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta"Circulation. 101. 1319-1323 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Miyamoto: "Changes in E-cadherin associated with cytoplasmic molecules in well and poorly differentiated endometrial cancer"Br.J.Cancer. 83. 1168-1175 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Ihara: "Crystallization and preliminary crystallographic analysis of the rho-binding domain of bovine rho-kinase"Acta.Crystallogr. D.Biol.Crystallogr.. 56. 1042-1044 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] P.A.Oude Weernink: "Stimulation of phosphatidylinositol-4-phosphate 5-kinase by Rho-kinase"J.Biol.Chem.. 275. 10168-10174 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Szaszi: "RhoA and rho kinase regulate the epithelial Na^+/H^+ exchanger NHE3. Role of myosin light chain phosphorylation"J.Biol.Chem.. 275. 28599-28606 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] R.Hashimoto: "Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term Potentiation"J.Neurochem.. 75. 373-382 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kanai-Azuma: "Co-localization of FAM and AF-6, the mammalian homologues of Drosophila faf and canoe, in mouse eye development"Mech.Dev.. 91. 383-386 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Hamaguchi: "Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N"Biochem. Biophys. Res.Commun.. 274. 825-830 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Fukata: "Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells"TRENDS in Pharm.Sci.. 22. 32-39 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Fukata: "Involvement of IQGAP1, an Effector of Rac1 and Cdc42 GTPases, in Cell-Cell Dissociation during Cell Scattering"Mol.Cell.Biol.. 21(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukata M.et al.: "Cell adhesion and & Rgr; small GTP ases"J.Cell Sci.. 112. 4491-4500 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukata M.et al.: "Cdc42 and Rac1 regulate the interaction of IQGAP1 with bata-catenin"J.Biol.Chem.. 274. 26044-26050 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukata M.et al.: "Phosphorylation of adducin by Rho-kinase plays a crucial rloe in cell motility"J.Cell Biol.. 145. 347-361 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kaibuchi K.et al.: "Regulation of cadherin-mediated cell-cell adhesion by the Rho family GTPases"Curr Opin Cell Biol. 11. 591-596 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kaibuchi K.: "Regulation of cytoskeleton and cell adhesion by Rho targets"Prog.Mol.Subcell.Biol.. 22. 23-38 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kaibuchi K.et al.: "Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells"Annu.Rev.Biochem. 68. 459-486 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawano Y.et al.: "Phosphorylation of myosin-binding subunit (MBS) of myosin phospgatase by Rho-kinase in vivo"J.Cell Biol.. 147. 1023-1038 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kosako H.et al.: "Specijic accumulation of Rho-associated kinase at the cleavage furrow during cytokinesis:cleavage furrow-specific phosphorylation of intermidiate filaments"Oncogene. 18. 2783-2788 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kuroda S.et al.: "Cdc42,Rac1,and their effector IQGAP1 as molecular switches for cadherin-mediated cell-cell adhesion"Biochem.Biophys.Res.Commun.. 262. 1-6 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maesaki R.et al.: "The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1"Mol.Cell. 4. 793-803 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maesaki R.et al.: "Biochemical and crystallographic characterization of a Rho effector domain of the protein serine/threonine kinase N in a complex with RhoA."J.Struct.Biol.. 126. 166-170 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mizuno T.et al.: "Identification and characterization of Drosohpila homolog of Rho-kinase"Gene. 238. 437-444 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimokawa H.et al.: "Rho-kinase-mediated pathway induces enhanced myosin light light chain phosphorylations in a swine model of coronary artery spasm"Cardiovasc.Res.. 43. 1029-1039 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Amano M.et al.: "The COOH terminus of Rho-kinase negatively regulates rho-kinase activity"J.Biol.Chem.. 274. 32418-32424 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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