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Regulation mechanism of a signal transduction by MUK-JNK pathway.

Research Project

Project/Area Number 14580685
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionYokohama City University

Principal Investigator

HIRAI Syu-ichi  Yokohama City University, School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (80228759)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordssignal transduction / cortex / JNK / migration / neuron / MUK / ノックアウトマウス / 細胞極性 / 微小管 / 神経細胞 / MAPキナーゼ
Research Abstract

c-Jun N-terminal kinase (JNK) is supposed to play fundamental roles in cellular events such as apoptosis and the establishment of planar cell polarity. To date, several MAP kinase kinase kinase (MAPKKK) class protein kinases are identified as upstream activator for JNK. However, when and how they become active in vivo to induce such cellular events via JNK have only partly been elucidated. Protein kinase MUK, also termed DLK or ZPK, is one of such MAPKKK class activator, which is highly expressed in neural tissues of mammals. To explore the significance of the MUK/DLK/ZPK-JNK signaling pathway in vivo, we first examined the expression of MUK/DLK/ZPK-JNK signaling pathway in vivo, we first examined the expression of MUK/DLK/ZPK protein and the distribution of active JNK in developing mouse at different embryonic stages. Immuno-histochemical staining, Western blot, and in-gel kinase assay revealed that the MUK protein level and JNK activity are enhanced potently in immature neurons crossing the intermediate zone of developing mouse neocortex. Adenovirus vector-mediated expression of exogenous MUK in neural precursor cells in utero impaired cell migration across the intermediate zone without affecting their viability and differentiation into immature neurons. Notably, MUK is associated with the particular structures, which are frequently located along microtubules and Golgi apparatus. Finally, loss of polarized organization of microtubules was frequently observed by the forced expression of MUK in culture cells. Taken together, these observations indicate that MUK-JNK pathway regulates neural cell migration in developing neocortex by controlling a cell polarity.

Report

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

    (9 results)

All Other

All Publications (9 results)

  • [Publications] S.Hirai et al.: "MAPK-upstream protein kinase (MUK) regulates the radial migration of immature neurons in telencephalon of mouse embryo."Development. 129. 4483-4495 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Manabe et al.: "Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells."Dev.Dyn.. 225. 61-69 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Hirai et al.: "MAPK-upstream protein kinase (MUK/DLK/ZPK) as a regulator of neural cell polarity in developing mouse neocortex."Eur.J.Biochem.. 270-S1. 183 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Hirai, A.Kawaguchi, M.Ono, D.F.Cui, R.Hirasawa, M.Baba, T.Ohnishi, S.Ohno.: "MAPK-upstream protein kinase (MUK/DLK/ZPK) as a regulator of neural cell polarity in developing mouse neocortex."Eur.J.Biochem.. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Manabe, S.Hirai, F.Imai, H.Nakanishi, Y.Takai, S.Ohno.: "Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells."Dev.Dyn.. 225. 61-69 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Hirai, A.Kawaguchi, R.Hirasawa, M.Baba, T.Ohnishi, S.Ohno: "MAPK-upstream protein kinase (MUK) regulates the radial migration of immature neurons in telencephalon of mouse embryo."Development. 129. 4483-4495 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Hirai et al.: "MAPK-upstream protein kinase (MUK/DLK/ZPK) as a regulator of neural cell polarity in developing mouse neocortex"European Journal of Biochemistry. 270・S1. 183 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirai, S. et al.: "MAPK-upstream protein kinase (MUK) regulates the radial migration of immature neurons in telencephalon of mouse embryo"Development. 129. 4483-4495 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Manabe, N. et al.: "Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells"Dev. Dyn.. 225. 61-69 (2002)

    • Related Report
      2002 Annual Research Report

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

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