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Study of the signal transduction mechanism for IL-2-induced T cell growth

Research Project

Project/Area Number 62480162
Research Category

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

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

SUGAMURA Kazuo  Tohoku University School of Medicine, 医学部, 教授 (20117360)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Masataka  Tohoku University School of Medicine, 医学部, 助手 (30180392)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,500,000 (Direct Cost: ¥4,500,000)
KeywordsIL-2 / IL-2 receptor / protein kinase C / cyclic AMP / TPA / 蛋白リン酸化 / IL-2 / IL-2受容体 / フォルボールエステル / リン酸化蛋白
Research Abstract

We demonstrated that IL-2 rapidly induced protein phosphorylation of a 67-kDa (pp67) and four 63 kDa (pp63s) cellular proteins in various t cells, and the IL-2-stimulated phosphorylation was mediated by th IL-2R -chain composed of the high affinity IL-2R. In addition, various phorbol esters and tumor promoters. which activate PKC, were also demonstrated to induce the phosphorylation of a pp67 and pp63s in these T cell lines. Therefore, the present study suggests that IL-2/IL-2R -chain interaction triggers the phosphorylation of pp67 and pp63s, where the PKC may have an important role.
On the other hand, a selected clone from an IL-2-dependent human T-cell line was persistently propagate in the presence of phorbol esters with the ability to activate protein kinase C (PKC), such as 12-0-tetradecanoylphorbol-13-acetate (TPA) or phorbol-12,13-dibutylate (PDBu). Thus, a TPA(PDBu)-dependent T-cell line, designated TPA-Mat, was established from an IL-2-dependent T cell line, ILT-Mat. The TPA-d … More ependency of TPA-Mat was not lost during cultivation for more than a year in the presence of TPA, and TPA-Mat cells still showed IL-2-dependent growth. However, the TPA(PDBu)-dependent growth of TPA-Mat did not seem to be mediate by an autocrine mechanism of IL-2 or by any other growth factor production, because these factors were not detected in TPA-Mat cell supernatants. Therefore, the phorbol esters substituted for IL-2 and may be directly involved in transduction of growth signals in TPA-Mat cells. Furthermore, the growth of TPA-Mat cells was stimulated not only by phorbol esters but also by nonphorbol ester tumor promoters with the ability to activate PKC. These observations suggest that the sustained activation of PKC by the phorbol esters could induce continuous growth of the IL-2-dependent TPA-Mat cells. Furthermore, we demonstrated that the PDBu-dependent growth of TPA-Mat cells was inhibited up to 90% by adenosine 3',5'-cyclic monophosphate (cAMP) raising agents such as forskolin, cholera toxin and 1-methl-3-isobutyl-xanthine, and cAMP analogues, whereas the IL-2-stimulated TPA-Mat growth was slightly inhibited. These findings suggest that the signal transduction pathway of PDBu-induced growth, which should involve activation of protein kinase C, is sensitive to cAMP, and that it cannot be exactly identical to the signal transdution pathway of IL-2-induced growth in TPA-Mat cells. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Hemmi,H.,et al.: J.Immunol.138. 664-666 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Matsuyama,M.,et al.: Microbiol.Immunol.31. 541-550 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Sakitani,M.,et al.: Virus genes. 1. 35-47 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ogawa,R.,et al.: J.Exp.Med.165. 959-969 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ogawa,R.,et al.: Bioch.Biophys.Res.Comm.144. 160-165 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ishii,T.,et al.: Bioch.J.242. 211-219 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tanaka,T.,et al.: Eur.J.Immunol.17. 1379-1382 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tanaka,T.,et al.: J.Immunol.140. 866-870 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ishii,T.,et al.: J.Immunol.141. 174-179 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fujii,M.,et al.: Microbiol.Immunol.32. 857-867 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Takeshita,T.,et al.: J.Cell.phys.136. 319-325 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Goto,Y.,et al.: FEBS Letters. 239. 165-168 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hemmi, H. et al.: "Lymphotoxin: Induction of terminal differentiation of the human myeloid leukemia lines HL-60 and THP-1." J. Immunol.138. 664-666 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Matsuyama, M. et al.: "Human T-lymphoblastoid cell lines with high- and low abilities to produce interferon-gamma constitutively and their susceptibilities to interferon." Microbiol. Immunol.31. 541-550 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Sakitani, M. et al.: "High affinity interleukin 2 receptors in HTLV-infected T cells can mediate signals for gene expression." Virus genes. 1. 35-47 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ogawa, R. et al.: "Tyrosine phosphorylation of an interleukin 2 receptor-like protein in cells transformed by human T-cell leukemia virus type I." J. Exp. Med.165. 959-969 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ogawa, R. et al.: "Tyrosine phosphorylation of interleukin 2 receptor-related protein in phytohemagglutinin-activated human lymphocytes." Bioch. Biphys. Res. Comm.144. 160-165 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] ISHI, T. et al.: "Characterization of interleukin 2 (IL-2)-stimulated protein phosphorylation in human T cells." Bioch. J.242. 211-219 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tanaka, T. et al.: "Functional interleukin 2 receptors on B cells lacking Tac antigens." Eur. J. Immunol.17. 1379-1382 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tanaka, T. et al.: "Novel receptor-mediated internalization of interleukin 2 in B cells." J. Immunol.140. 866-870 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ishii, T. et al.: "Protein phosphorylation mediated by IL-2/IL-2 receptor -chain interaction." J. Immunol.141. 174-179 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fujii, M. et al.: "Selective inhibition of high- but not low-affinity interleukin 2 binding by lectins and anti-interleukin 2 receptor antibody." Microbiol. Immunol.32. 857-867 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Takeshita, T. et al.: "Phorbol esters can persistently replace interleukin-2 (IL-2) for the growth of a human IL-2-dependent T-cell line." J. Cell. Phys.136. 319-325 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Goto, Y. et al.: "Adenosine 3',5'-cyclic monophosphate (CAMP) inhibits phorbol ester-induced growth of an IL-2-dependent T cell lines." FEBS Letters. 239. 165-168 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tanaka,T.;et al.: J.Immunol.140. 866-870 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Ishii,T.;et al.: J.Immunol.141. 174-179 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Fujii,M;et al.: Microbiol.Immunol.32. 857-867 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Takeshita,T.;et al.: J.Cell.Phys.136. 319-325 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Goto,Y.;et al.: FEBS Letters. 239. 165-168 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Ohtani.K;Nakamura.M;Saito.S;Noda.T;Ito.Y;Sugamura.K;Hinuma.Y: EMBO J. 6. 389-395 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Ogawa.R;Sugamura.K;Watanabe.K: J.Exp.Med. 65. 959-969 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hemmi.H;Nakamura.T;Tamura.K;Shimizu.Y;Kato.S;Miki.T;Takahashi.N;Muramatsu.M;Numano.N;Sugamura.K: J.Immunol. 138. 664-666 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Ishii.T;Kohno.M;Nakamura.M;Hinuma.Y;Sugamura.K: Bioch.J. 242. 211-219 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Takeshita.T;Goto.Y;Nakamura.M;Fujii.M;Iwami.M;Hinuma.Y;Sugamura.K: J.Cell.physiol.

    • Related Report
      1987 Annual Research Report
  • [Publications] Ishii.K;Takeshita.T;Nunata.N;Sugamura.K: J.Immunol.

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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