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Dynamics of MAP kinase cascade in immune response

Research Project

Project/Area Number 14572036
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionNagoya City University

Principal Investigator

SUZUKI Ryo  Nagoya City University, Graduate of Pharmaceutical Sciences, Lecturer, 大学院・薬学研究科, 助手 (00344458)

Co-Investigator(Kenkyū-buntansha) HIRASHIMA Naohide  Nagoya City University, Graduate of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (10192296)
NAKANISHI Marnoru  Nagoya City University, Graduate of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (90090472)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsMAP kinase cascade / Mast Cell / Immune Response / Fluorescent Protein / Confocal Laser Scanning Microscopy / Membrane Translocation / Nuclear shuttling / Nuclear Export Signal / 蛍光蛋白質GFP
Research Abstract

The MAP kinase cascade is essential for signaling of various extracellular stimuli to the nucleus. Stimulation of T cells, B cells, and mast cells through aggregation of antigen receptors and other stimulants results in activation of MAP kinase. In this study, we focused on the dynamics of MAP kinase (MAPK) cascade protein in mast cells using yellow fluorescent protein (YFP)-tagged MAPK (ERK2) and YFP-tagged MAPKKK (Raf-1). Here, we have shown many aspects of MAP kinase signaling in immune response.
1.In wild type mast cells, the membrane translocation of MAPKKK (Raf-1) reached 〜3 min after antigen stimulation, and thereafter the nuclear import of MAPK (ERK2) reached the maximum at 5〜7 min Raf-1 did not co-localize with lipid microdomain.
2.In the presence of leptomycin B (inhibitor of nuclear export), the export of ERK2 became more slowly though ERK2 was imported to the nucleus as like as in non-treated cells.
3.We have studied the effects of FcγRIIB on the FcεRI-mediated nuclear shuttling of MAP kinase in immune cells. The co-clustering of FcεRI and FcγRIIB increased the [Ca-<2+>]_i and induced the nuclear import of ERK2. However, the calcium increase was transient and ERK2 was rapidly exported to the cytoplasm.
4.We have studied the effects of two tyrosine phosphatases, HePTP (a tyrosine-specific phosphatase) and VHR (a dual specificity protein-tyrosine phosphatase), on the FcεRI-mediated nuclear shuttling of ERK2 in the mast cells. In HePTP-overexpressing cells, the maximal amount of ERK2 accumulated in the nucleus was much less than that in wild type cells though the nuclear import of ERK2 reached the maximum in the similar time-course. In VHR-overexpressing cells, the amount of imported ERK2 decreased more rapidly though ERK2 was imported to the nucleus as like as in wild type cells.
Thus we succeeded to show the molecular mechanism of MAP kinase cascade protein in immune response.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Mori, N., Suzuki, R., et al.: "Nerve-mast cell (RBL) interaction : RBL membrane ruffling occurs at the contact site with an activated neurite."Am.J.Physiol.Cell Physiol.. 283(6). C1738-C1744 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中西守, 鈴木亮: "免疫系と超分子システム"化学工業. 53. 472-475 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Komano, H., Shiraishi, H., et al.: "A new functional screening system for identification of regulators for the generation of amyloid β-protein."J.Biol.Chem.. 277. 39627-39633 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sai, X., Kawamura, Y., et al.: "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid β-protein."J.Biol.Chem.. 277. 12915-12920 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori N, Suzuki R, Furuno T, McKay DM, Wada M, Teshima R, Bienenstock J, Nakanishi M.: "Nerve-mast cell (RBL) interaction : RBL membrane ruffling occurs at the contact site with an activated neurite."Am.J.Physiol. Cell Physiol.. 283. C1738-C1744 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakanishi, M., Suzuki, R.: "The nerve-immune crosstalk as a supermolecular system."Kagaku Kogyo (Article in Japanese). 53. 472-475 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Komano H, Shiraishi H, Kawamura Y, Sai X, Suzuki R, Serneels L, Kawaichi M, Kitamura T, Yanagisawa K.: "A new functional screening system for identification of regulators for the generation of amyloid beta-protein."J.Biol.Chem.. 277. 39627-39633 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sai X, Kawamura Y, Kokame K, Yamaguchi H, Shiraishi H, Suzuki R, Suzuki T, Kawaichi M, Miyata T, Kitamura T, De Strooper B, Yanagisawa K, Komano H.: "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein."J.Biol.Chem.. 277. 12915-12920 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori, N., Suzuki, R., et al.: "Nerve-mast cell(RBL) interaction : RBL membrane ruffling occurs at the contact site with an activated neurite."Am.J.Physiol.Cell Physiol.. 283(6). C1738-C1744 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中西 守, 鈴木 亮: "免疫系と超分子システム"化学工業. 53. 472-475 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Komano, H., Shiraishi, H., et al.: "A new functional screening system for identification of regulators for the generation of amyloid β-protein."J.Biol.Chem.. 277. 39627-39633 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sai, X., Kawamura, Y., et al.: "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid β -protein."J.Biol.Chem.. 277. 12915-12920 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoko Mori: "Nerve-mast cell (RBL) interaction : RBL membrane ruffling occurs at the contact site with an activated neurite"American Journal of Physiology. 283・6. C1738-C1744 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中西 守: "免疫系と超分子システム"化学工業. 53. 472-475 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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