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GTP-binding Proteins as Cellular Signal Transducer

Research Project

Project/Area Number 05271101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionThe Tokyo Metropolitan Institute of Medical Science (1995-1996)
The Institute of Physical and Chemical Research (1993-1994)

Principal Investigator

UI Michio  The Tokyo Metropolitan Institute of Medical Science, Director, 所長 (50001037)

Co-Investigator(Kenkyū-buntansha) FUJIOKA Toshiyuki  Inst.Phys.Chem.Res. (RIKEN), Researcher, 研究員 (20133770)
NOZAWA Yoshinori  Gofu Univ.Med.School, Professor, 医学部, 教授 (10021362)
KATADA Toshiaki  The Univ.Tokyo, Fac.Pharm.Sci., Professor, 薬学部, 教授 (10088859)
高井 義美  大阪大学, 医学部, 教授 (60093514)
日高 弘義  名古屋大学, 医学部, 教授 (80100171)
Project Period (FY) 1993 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥117,300,000 (Direct Cost: ¥117,300,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1995: ¥41,300,000 (Direct Cost: ¥41,300,000)
Fiscal Year 1994: ¥33,400,000 (Direct Cost: ¥33,400,000)
Fiscal Year 1993: ¥39,600,000 (Direct Cost: ¥39,600,000)
KeywordsHeterotrimeric G-protein / Ras protein family / Growth factor / PtdIns 3-kinase / Protein tyrosine kinase / Gbetagamma subunit / Wortmannin / Membrane receptor / Cβγサブユニット / ras蛋白質ファミリー / インシュリン / 活性酸素生成 / 走化性ペプチド
Research Abstract

This research project, entitled "GTP-binding Proteins as Cellular Signal Transducer" and supported by Grant-in-Aid for Scientific Research on Priority Areas, consisted of two groups with the following research subjects, i, e., the first group with "Mechanisms and Roles of alphabetagamma-Hetero-trimeric G-Proteins" ant the second group with "Mechanisms and Roles of Low-molecular GTP-binding proteins". Although both of these big families of GTP-binding proteins play essential roles in membrane receptor-initiated intracellular signaling network, their functions as signaling proteins are distinctly different from each other. The former is coupled to, and mediated all the intracellular signals triggered by, receptors whose common protein structure is characterized by particular seven membrane-spanning helical domains and whose physiological agonists include essentially all of neurotransmitters, neuropeptides and protein hormones (except insulin). The latter plays a pivotal role in intracell … More ular signaling cascades arising from stimulation of receptors for growth factors (including insulin), cytokines and other autacoids. These receptors are distinctly different from heterotrimeric G-protein-coupled receptors in structure and function ; the receptor proteins possess tyrosine kinase domains or, alternatively, though having no endogenous kinase activity, activate non-receptor-type protein tyrosine kinases at the first step of triggered intracellular signaling. The low-molecular GTP-binding proteins, such as Ras, Rho.Rab and other subfamilies, function to link these signaling eventually to cell proliferation, gene expression, morphological changes, cell-cell contact and intracellular protein traffics. All the investigators belonging to either of these two groups of the project have made their own original contributions in these internationally very competitive fields of research. Particularly striking contributions were those made by the head investigator of the project and his colleagues. They have proposed new mechanisms, related to PtdIns 3-kinase, of the "crosstalk" between these two different signaling systems. Less

Report

(5 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Matsuo,T.,K.Hazeki,O.Hazeki,T.Katada and M.Ui: "Activation of phosphatidylinositol 3-kinase by concanavalin A through dual signaling pathways,G protein-coupled and phosphotyrosine-related,and an essential role of the G protein-coupled signals for the lectin-induced respiratory burst in human monocytic THP-1 cells." Biochem.J.315. 505-512 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuo,T.,K.Hazeki,O.Hazeki,T.Katada and M.Ui: "Specific association of phosphatidylinositol 3-kinase with the protooncogene product Cbl in Fcγ receptor signaling." FEBS Lett.382. 11-14 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okada,T.,O.Hazeki,M.Ui and T.Katada: "Synergistic activation of PtdIns 3-kinase by insulin and fMLP in intact THP-1 cells." Biochem.J.317. 475-480 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kajiyama,Y.,Y.Sanai and M.Ui: "A role of asialoglycoproteins for plasma-membrane-induced inhibition of the switching from α_1-to β-subtypes in adrenergic response during primary culture of rat hepatocytes." Biochem.J.316. 743-749 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suzuki,T.,O.Hazeki,K.Hazeki,M.Ui,and T.Katada: "Involvement of the βγ subunits of inhibitory GTP-binding protein in chemoattractant receptor-mediated potentiation of cyclic AMP formation in guinea pig neutrophils." Biochim.Biophys.Acta. 1313. 72-78 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuo,T.,K.Hazeki,N.Tsujimoto,S.I.Inoue,H.Kurosu,K.Kontani,O.Hazeki,M.Ui,and T.Katada: "Association of phosphatidylinositol 3-kinase with the proto-oncogene product Cbl upon CD38 ligation by a specific monoclonal antibody in THP-1 cells." FEBS Lett.397. 113-116 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 宇井理生: "(新臨床医のための分子医学シリーズ)細胞内情報伝達のしくみ 細胞内シグナル伝達の基本的原理" 羊土社, 12 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 佐々木雄彦、櫨木 修、堅田利明、宇井理生: "タンパク質の分子間相互作用実験法 wortmanninとPI3-キナーゼ" 羊土社, 8 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Im, D.S., T.Fujioka, T.Katada, Y.Kondo, M.Ui and F.Okajima: "Characterization of sphingosine 1-phosphate-induced actions and its signaling pathways in rat hepatocytes." Amer J.Physiol Gastrointest. L35. G1091-G1099 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishii, I., T.Izumi, H.Tsukamoto, H.Umeyama, M.Ui and T.Shimizu: "Alanine exchanges of polar amino acids in the transmembrane domains of a platelet-activating factor receptor generate both constitutively active and inactive mutants." J.Biol.Chem.272. 7846-7854 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuo, T., K.Hazeki, N.Tsujimoto, S.I.Inoue, H.Kurosu, K.Kontani, O.Hazeki, M.Ui and T.Katada: "Association of phosphatidylinositol 3-kinase with the proto-oncogene product Cb1 upon CD38 ligation by a specific monoclonal antibody in THP-1 cells." FEBS Lett.397. 113-116 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kazeki.O., K.Hazeki, T.Katada and M.Ui: "Inhibitory effect of wortmannin on phosphatidylinositol 3-kinase-mediated cellular events." J.Lipid Mediators Cell Signal. 14. 259-261 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suzuki, T., O.Hazeki, K.Hazeki, M.Ui and T.Katada: "Involvement of the betagamma subunits of inhibitory GTP-binding protein in chemoattractant receptor-mediated potentiation of cyclic AMP formation in guinea pig neutrophils." Biochim.Biophys.Acta. 1313. 72-78 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tada, S., J.Yanagisawa, T.Sonoyama, A.Miyajima, M.Seki, M.Ui and T.Enomoto: "Characterization of the properties of a human homologue of Escherichia coli RecQ from xeroderma pigmentosum group C and from HeLa cells." Cell Struct.Funct.21. 123-132 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ueda, H., S.Tamura, N.Fukushima, T.Katada, M.Ui and M.Satoh: "Inositol 1,4,5-trisphosphate-gated calcium transport through plasma membranes in nerve terminals." J.Neurosci.16. 2891-2900 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okada, T., O.Hazeki, M.Ui and T.Katada: "Synergistic activation of PtdIns 3-kinase by tyrosine-phosphorylated peptide and betagamma-subunits of GTP-binding proteins." Biochem.J.317. 475-480 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kajiyama, Y., Y.Sanai and M.Ui: "A role of asialoglycoproteins for plasma-membrane-induced inhibition of the switching from alpha1-to beta-subtypes in adrenergic response during primary culture of rat hepatocytes." Biochem.J.316. 743-749 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sasaki, T., K.Hazeki, O.Hazeki, M.Ui and T.Katada: "Focal adhesion kinase (p125^<FAK>) and paxillin are substrates for sphingomyelinase-induced tyrosine phosphorylation in Swiss 3T3 fibroblasts." Biochem.J.315. 1035-1040 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ueda, H., H.Misawa, N.Fukushima, T.Katada, M.Ui and M.Satoh: "A subtype of k-opioid receptor mediates inhibition of high-affinity GTPase inherent in Gil in guinea pig cerebellar membranes." J.Neurochem.66. 845-851 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuo,T.,K.Hazeki,O.Hazeki,T.Katada and M.Ui: "Activation of phosphatidylinositol 3-kinase by concanavalin A through dual signaling pathways,G protein-coupled and phosphotyrosine-related,and an essential role of the G protein-coupled signals for the Iectin-induced respiratory burst in human monocytic THP-1 cells." Biochem.J.315. 505-512 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuo,T.,K.Hazeki,O.Hazeki,T.Katada and M.Ui: "Specific association of phosphatidylinositol 3-kinase with the protooncogene product Cbl in Fcγreceptor signaling." FEBS Lett.382. 11-14 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okada,T.,O.Hazeki,M.Ui and T.Katada: "Synergistic activation of PtdIns 3-kinase by insulin and fMLP in intact THP-1 cells." Biochem.J.317. 475-480 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kajiyama,Y.,Y.Sanai and M.Ui: "A role of asialoglycoproteins for plasma-membrane-induced inhibition of the switching from α_1-to β-subtypes in adrenergic response during primary culture of rat hepatocytes." Biochem.J.316. 743-749 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzuki,T.,O.Hazeki,K.Hazeki,M.Ui,and T.Katada: "Involvement of the βγ subunits of inhibitory GTP-binding protein in chemoattractant receptor-mediated potentiation of cyclic AMP formation in guinea pig neutrophils." Biochim.Biophys.Acta. 1313. 72-78 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuo,T.,K.Hazeki,N.Tsujimoto,S.I.Inoue,H.Kurosu,K.Kontani,O.Hazeki,M.Ui,and T.Katada: "Association of phosphatidylinositol 3-kinase with the proto-oncogene product Cbl upon CD38 ligation by a specific monoclonal antibody in THP-1 cells." FEBS Lett.397. 113-116 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 宇井理生: "(新臨床医のための分子医学シリーズ)細胞内情報伝達のしくみ細胞内シグナル伝達の基本的原理" 羊土社, 12 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 佐々木雄彦、櫨木 修、堅田利明、宇井理生: "タンパク質の分子間相互作用実験法 wortmannin と PI3-キナーゼ" 羊土社, 8 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Misawa, H., H. Ueda, T. Katada, M. Ui, and M. Satoh: "A subtype of opioid kappa-receptor is coupled to inhibition of Gil-mediated phospholipase C activity in the guinea pig cerebellum." FEBS Lett.361. 106-110 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ui, M., T. Okada, K. Hazeki, and O. Hazeki: "Wortmannin as a unique probe for an intracellular signalling protein, phosphoinositide 3-kinase." Trends Biochem. Sci.20. 303-307 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ahmed, M. U., K. Hazeki, O. Hazeki, T. Katada, and M. Ui: "Cyclic AMP-increasing agents interfere with chemoattractant-induced respiratory burst in neutrophils as a result of the inhibition of phosphatidylinositol 3-kinase rather than receptor-operated Ca^<2+> influx." J. Biol. Chem.270. 23816-23822 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sasaki, T., K. Hazeki, O. Hazeki, M. Ui, and T. Katada: "Permissive effect of ceramide on growth factor-induced cell proliferation." Biochem. J.313. 829-834 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsuo, T., K. Hazeki, O. Hazeki, T. Katada and M. Ui: "Activation of phosphatidylinositol 3-kinase by concanavalin A through dual signaling pathways, G protein-coupled and phos photyrosine-related, and an essential role of the G protein-coupled signals for the lectin-induced respiratory burst in hu man monocytic THP-1 cells." Biochem. J.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsuo, T., K. Hazeki, O. Hazeki, T. Katada and M. Ui:"Specific association of phosphatidylinositol 3-kinase with the protooncogene product Cbl in Fcγ receptor signaling." FEBS Lett.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 宇井理生(編著): "廣川ニューロサイエンス 情報変換物質-G蛋白質" 廣川書店, 166 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 宇井理生(編著): "バイオマニュアルUPシリーズ シグナル伝達実験法" 羊土社, 267 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hazeki,K.,T.Seya,O.Hazeki and M.Ui: "Involvement of the pertussis toxin-sensitive GTP-binding protein in regulation of wxpression and function of granulocyte somplement receptor type 1 and type 3." Mol.Immunol.31. 511-518 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ishii,I.,and M.Ui: "Possible involvement of GTP-binding proteins in 1 alpha,25-dihydroxyvitamin D-3 induction of tissue transglutaminase in mouse peritoneal macrophages." Biochem.Biophys.Res.Commun.203. 1773-1780 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ishii,I.,and M.Ui: "Retinoic acid-induced gene expression of tissue transglutaminase via protein kinase C-dependent pathway in mouse peritoneal macrophages." J.Biochem.115. 1197-1202 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kajiyama,Y.,and M.Ui: "Switching from alpha(1)-to beta-subtypes in adrenergic response during primary culture of adult-rat hepatocytes as affected by the cell-to-cell interaction through plasma membranes." Biochem.J.303. 313-321 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ninomiya,N.,K.Hazeki,Y.Fukui,T.Seya,T.Okada,O.Hazeki.and M.Ui: "Involvement of phosphatidylinositol 3-kinase in Fc gamma receptor signaling." J.Biol.Chem.269. 22732-22737 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Uehara,T.,S.Hoshino,M.Ui,Y.Tokumitsu,and Y.Nomura: "Possible involvement of phosphatidylinositol-specific phospholipase Cralated to pertussis toxin-sensitive GTP-binding proteins during adipocyte differentiation of 3T3-L1 fibroblasts:Negative regulation of protein kinase C." Biochim.Biophys.Acta. 1224. 302-310 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 宇井理生: "生体膜を介する情報伝達" 講談社サイエンティフィック(予定), 550 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 宇井理生(編著): "GTP結合蛋白質-情報伝達を抑制する分子スイッチ" メジカルビュー社, 207 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Banno,et al.: "Potentiation by Cholera Toxin of Bradykinin-Induced Inoslitolte…" Bliochem J.292. 401-408 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] F.Kanai,et al.: "Insulin-Stimulated GLUT4 Translocation Is Relevant to the…" Biochem Biophys Res Commun.195. 762-768 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Kontani,et al.: "NAD Glycohydrolase Specifically Induced by Retinoic Acid in…" J Biol Chem.268. 16895-16898 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Okada,et al.: "Blockage of chemotactic peptide-induced stimulation of neutrophils…" J.Biol.Chem.269. 3563-3567 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Okada,et al.: "Essential role of phosphatidylinositol 3-kinase in insulin-induced…21GC05:J.Biol.Chem." 269. 3568-3573 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Toratani,et al.: "Production of Monoclonal Antibodies That Inhibit ADP-Ribosylation…" FEBS Lett.324. 353-357 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2018-07-06  

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