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Signal Transduction Systems for Cell Proliferation, Differentiation and Adhesion with Emphasis upon the Role of GTP-binding Proteins

Research Project

Project/Area Number 04404091
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 代謝生物化学
Research InstitutionThe Institute of Physical and Chemical Chemical Research (RIKEN) (1993-1994)
The University of Tokyo (1992)

Principal Investigator

UI Michio  The Institute of Physical and Chemical Research, Chief Researcher, 宇井特別研究室, 特別招聘研究員 (50001037)

Co-Investigator(Kenkyū-buntansha) HAZEKI Kaoru  The Institute of Physical and Chemical Research, Researcher, 宇井特別研究室, 研究員 (50146007)
多田 周右  東京大学, 薬学部, 助手 (00216970)
星野 真一  東京大学, 薬学部, 助手 (40219168)
櫨木 修  東京大学, 薬学部, 助手 (80142751)
榎本 武美  東京大学, 薬学部, 助教授 (80107383)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥29,000,000 (Direct Cost: ¥29,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1992: ¥17,000,000 (Direct Cost: ¥17,000,000)
Keywordsheterotrimeric G proteins / cell differentiation / cell adhesion / wortmannin / PI 3-kinase / protein tyrosine phosphorylation / pertussis toxin / adrenergic receptor / 3量体G蛋白質 / 肝臓初代培養 / betaアドレナリン受容体 / alpha_1アドレナリン受容体 / Gs / Gq / G蛋白質 / Caチャネル / 肝蔵細胞 / 細胞分化 / HL-60細胞 / 3T3細胞 / 百日咳毒素
Research Abstract

Most parts of the present research depend on two experimental systems : i.e., primary cultured rat hepatocytes and phagocytes from guinea pig peritoneal fluids or cultured cell lines. The adult liver cells retained their differentiated liver functions during primary culture at the high-cell densities, whereas they entered the cell cycle or underwent proliferation exhibiting active DNA systhesis when cultured at the low-cell densities. As regards adrenergic receptor subtypes, the alpha_1-receptor-mediated signal was one of the differentiated liver functions ; beta_2-receptor-mediated cell responses developed quickly, at the expense of alpha_1-receptor-mediated ones, upon the G_0-to-G_1/S phase transition in the cell cycle. The development of beta_2-responses was inhibited by addition of the cell membrane fraction into the low-cell density culture, indicating essential roles of the cell adhesion via cell surface glycoproteins. Activation of glycogen phosphorylase, the eventual cell respo … More nse to either alpha_1-or beta_2-receptor stimulation, was never inhibited by wortmannin, a selective inhibitor of phosphatidylinositol (PI) 3-kinase, when the latter subtype receptors were stimulated. In contrast, wortmannin was partially inhibitory to the cell response to alpha_1-receptor stimulation, being suggestive of occurrence of dual signaling systems, PI 3-kinase-dependent and -independent, in alpha_1-receptor initated Ca^<2+> signaling. In the case of phagocytes whose major functions inclde chemotaxis via cell-to-cell adhesion, we found, taking advantage of wortmannin again, PI 3-kinase to play an essential role in Fcgamma receptor-initiated signalng that is characterized by predominance of protein tyrosine kinase systems. A proten with a molcular weight of 115 kDa, tyrosine-phosphorylated upon the receptor stimulation, bound to the p85-regulatory subunit of PI 3-kinase, probably as a physiological activator of PI 3-kinase inphagocytes. This novel finding will afford an important problem to be solved in future studies. Stimulation of CR3, a complement receptor coupled to a pertussis toxin-susceptible heterotrimeric G protein, or concanavalin A receptors, consisting of the two types of G protein-coupled and non-coupled ones, gave rise to phagocytosis in a wortmannin-sensitive manner, providing evidence for involvement of PI 3-kinase in these signaling systems, too. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Hazeki,K.,T.Seya,O.Hazeki,and M.Ui: "Involvement of the pertussis toxin-sensitive GTP-binding protein in regulation of expression and function of granulocyte complement receptor type1 and type 3." Mol.Immunol.31. 511-518 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Uehara,T.,S.Hoshino,M.Ui,Y.Tokumitsu,and Y.Nomura: "Possible involvement of phosphatidylinositol-specific phospholipase C related 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 宇井理生(編著): "GTP結合蛋白質-情報伝達を制御する分子スイッチ" メジカルビュー社, 207 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hazeki, K., T.Seya, O.Hazeki, and M.Ui :"Involvement of the pertussis toxin-sensitive GTP-binding protein in regulation of expression and function of granulocyte complement receptor type 1 and type 3." Mol.Immunol.31 :. 511-518 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Uehara, T., S.Hoshino, M.Ui, Y.Tokumitsu, and Y.Nomura :"Possible involvement of phosphatidylinositol-specific phospholipase C related 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hazeki,K.,T.Seya,O.Hazeki,and M.Ui: "Involvement of the pertussis toxin-sensitive GTP-binding protein in regulation of expression and function of granulocyte complement 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.Seva,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 Crelated to pertussis toxin-sensitive GTP-binding proteins during adipocyte differertiation of 3T3-L 1 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, 550 (1995)

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

    • Related Report
      1994 Annual Research Report
  • [Publications] 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.Matsumoto,et al.: "TAF-I ,a novel host factor required to stimulate the adenovirus core・・・" J.Biol.Chem.268. 10582-10587 (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・・・" J.Biol.Chem.269. 3568-3573 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arata,Y.et al.: "Probable occurrence of toxin-susceptible G proteins in the nematode Caenorhaditis elegans." FEBS Lett.300. 73-76 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tada,S.et al.: "P_2-Purinoceptor-mediated cyclic AMP accumulation in bovine vascular smooth muscle cells." Eur.J.Pharmacol.227. 25-31 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yanagisawa,J.et al.: "Alteration of a DNA-dependent ATPase activity in xeroderma pigmentosum complementation group C cells." J.Biol.Chem.267. 3585-3588 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yatomi,Y.et al.: "Phosphorylation of the inhibitory guanine-nucleotidebinding protein as a possible mechanism of inhibition by protein kinase C of agonist-induced Ca^<2+> mobilization in human platelet." Eur.J.Biochem.205. 1003-1009 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yatomi,Y.et al.: "Suppression by wortmannin of platelet responses to stimuli due to inhibition of pleckstrin phosphorylation." Biochem.J.285. 745-751 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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