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Cell growth and second messengers

Research Project

Project/Area Number 04454071
Research Category

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

Allocation TypeSingle-year Grants
Research Field 応用生物化学・栄養化学
Research InstitutionThe University of Tokyo

Principal Investigator

FUKUI Yasuhisa  Tokyo Univ.Agriculture Associate Prof., 農学部, 助教授 (00181248)

Co-Investigator(Kenkyū-buntansha) ONODERA Kazukiyo  Tokyo Univ.Agriculture Profossor, 農学部, 教授 (90012773)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsSecond Messenger / PI3 kinase / Monoclonal Antibodios / Osteoclasts / ホスファチジルイノシトール3キナーゼ / サブユニット / 増殖因子 / ホスファターゼ / ホスファチジルイノシトール / アフェニティ精製
Research Abstract

We studied about cell responses after growth factor or differentiation factor stimulation on the aspect of synthesis of second messengers. Especially on phosphatidylinositol-3 kinase (PI3K), which is activated immediately after growth factor stimulation. First, to see the role of each domains, we produced the monoclonal antibodies to the various part of the 85kD subunit (p85). We have previously produced the antibodies to amino-terminal two third of the alpha type p85, however, there were no antibodies to the carboxyl-terminal portion of p85. We made such antibodies by immunizing mice with the peptides the corresponding to carboxyl-terminal portion of p85. Using the obtained antibodies, we analyzed the expression of p85 in various cell lines obtained from human cancers. One of the cell lines, HCC2998, expressed the smaller p85s instead of the wild type. The study on relationship between cell transformation and the mutation is now underway. For another subunit, p110, we have not succeeded in the production of the monoclonal antibodies.
We also studied on the role of PI3K in osteoclasts. Inhibition of PI3K by a specific inhibitor, wortmannin, resulted in blockage of bone resorption.It appeared that the ruffled borders were not formed after inhibition of Pl3K.At the same time, the podosome, an F-actin structure specifically formed in osteoclasts, was lost. Stress fibers in the fibroblasts were not affected. These results suggest that the actin rearrangement is controlled strictly and that PI3K is involved in the control. The relationship between formation of podosomes and ruffled border is being studied.

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Taro Okada 他: "Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selsctive inhibition of phosphatidylinositol 3-kinase." J.Biol.Chem. 269. 3536-3567 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koutaro Kimura 他: "Neurite outgrowth of PC12 cell is suppressed by wortmannin,a specific inhibition of phosphatidylinositol 3-kinase." J.Biol.Chem. 269. 18961-18967 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Noriyuki Ninomiya 他: "Involvement of phosphatidylinositol 3-kinase in Fcγ receptor singnaling" 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] Sakda Daduang 他: "Production of monoclonal antibodise specific to carboxyl terminal region of 85kDa subunit of phosphatidylinositol 3-kinase." immun Cell Biol. (発売予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koutaro Kimura 他: "phosphatidylinositol 3-kinase in fission yeast:A possible role in stress responses." Bisci Biotech Biochem. (発売予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Nakamura 他: "Wortmannin,a specific inhibitor of phosphatidylinositol 3-kinase,block osteoclastic bone resorption." FEBS Letter. (発売予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taro Okada et al.: "Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase." J.Biol.Chem.269. 3563-3567 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koutaro Kimura et al.: "Neurite outgrowth of PC12 cells is suppressed by wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase." J.Biol.Chem.269. 189961-18967 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Noriyuki Ninomiya et al.: "Involvement of phosphatidylinositol 3-kinase in Fcgamma 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] Sakda Daduang et al.: "Production of monoclonal antibodies specific to carboxyl terminal region of 85kDa subunit of phosphatidylinositol 3-kinase." Immun.Cell Biol.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koutarou Kimura et al.: "Phosphatidylinositol-3 kinase in fission yeast : A possible role in stress responses." Biosci.Biotech.Biochem.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Nskamura et al.: "Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption." FEBS Letters. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taro Okada,他: "Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase." J.Biol.Chem.269. 3563-3567 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Koutaro Kimura,他: "Neurite outgrowth of PC12 cells is suppressed by wortmannin,a specific inhibitor of phosphatidylinositol-3 kinase." J.Biol.Chem.269. 18961-18967 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Noriyuki Ninomiya,他: "Involvement of phosphatidylinositol 3-kinase in Fcg receptor signaling." J.Biol.Chem.269. 22732-22737 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sakda Daduang,他: "Production of monoclonal antibodies specific to carboxyl terminal region of 85kDa subunit of phosphatidylinositol 3-kinase." Immun.Cell Biol.71(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Koutaro Kimura,他: "Phosphatidylinositol-3 kinase in fission yeast:A possible role in stress responses." Biosci.Biotech.Biochem. (発表予定).

    • Related Report
      1994 Annual Research Report
  • [Publications] Ichiro Nakamura,他: "Phosphatidylinositol-3 kinase is involved in osteoclastic bone resorption." FEBS Letters. (発表予定).

    • Related Report
      1994 Annual Research Report
  • [Publications] 岡田太郎: "Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase." J.Biol.Chem.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 矢野浩史: "Inhibition of histamine secretion by wortmannin through the blockage of phosphatidylinositol 3-kinase in RBL-2H3 cells." J.Biol.Chem.268. 25846-25856 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 芝崎太: "Differential properties of monomer and heterodimer forms of phosphatidylinositol 3-kinases." J.Biochem.289. 227-231 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 田中伸哉: "Structure of 85kDa Subunit of Human Phosphatidylinositol 3-kinase analyzed by monoclonal antibodies." Jap.J.Cancer.Res.84. 279-289 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 山梨 裕二 他6名: "Activation of src-like protein-tyrosine kinase Lynand its association with phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling." Proc.Natt.Acad.USA. 89. 1118-1122 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 林 日出喜 他7名: "Insulin treatment stimulates the tyrosine phosphorylation of the a-type 85-kDa subunit of phosphatidylinositol 3-kinase in vivo." J.Biol.Chem.267. 22575-22580 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 芝崎 太 他2名: "Differential properties of monomer and heterodimer forms of phosphatidylinositol 3-kinases." J.Biochem. 発表予定.

    • Related Report
      1992 Annual Research Report
  • [Publications] 米沢 一仁 他16名: "Insuliun-dependent formation of a complex containing 85-kDa subunit of P13-kinase and tyrosine-phosphorylated IRS-1." J.Biol.Chem. 267. 25958-25996 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 田中伸哉 他6名: "Structure of 85kDa Subunit of Human Phosphatidylinositol 3-kinase analyzed by monoclonal antibodies." Jap.J.Cancer Res.

    • Related Report
      1992 Annual Research Report

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

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