初期発生期におけるJNKシグナル伝達経路の多様な生理的役割  [in Japanese] Diverse physiological functions of JNK signaling networks during early embryogenesis  [in Japanese]

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Author(s)

    • 浅岡 洋一 ASAOKA Yoichi
    • 東京医科歯科大学 難治疾患研究所 発生再生生物学分野 Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University

Abstract

c-Jun N-terminal kinase(JNK)シグナル伝達経路は,細胞外からの様々なストレス刺激や発生プログラムなどの内因性シグナルを細胞核へ的確に伝達するための主要なシステムの1つである。JNKはMAPキナーゼファミリーに属するタンパク質リン酸化酵素であり,線虫から哺乳類に至る動物門で幅広く保存されている。JNKは上流の2種類の活性化因子であるMAPキナーゼキナーゼ(MKK)4とMKK7によってリン酸化を受けて活性化し,遺伝子発現を調節することにより多彩な細胞応答を誘導する。近年,MKK4とMKK7のそれぞれのノックアウトマウスを用いた解析から,これらが発生期の肝臓形成や脳形成に重要な役割を果たすことが明らかとなった。一方,JNKシグナルは器官形成期より早い時期の形態形成運動にも関与することが最近になって示され,初期胚のボディプラン形成におけるJNKの役割が注目を集めている。本稿では,MKK4とMKK7の生化学的特性について概説するとともに,各動物種の初期胚形成期における両キナーゼの生理機能を比較し,最後にJNKシグナルが形態形成運動を統御する分子機構の一端についてゼブラフィッシュの知見を中心に紹介する。

The c-Jun N-terminal kinase(JNK), which belongs to the mitogen-activated protein kinase family, plays important roles in a broad range of physiological processes. JNK is controlled by two upstream regulators, mitogen-activated protein kinase kinase(MKK)4 and MKK7, which are activated by various MAPKKKs. These two MAPKKs directly phosphorylate specific Tyr and Thr residues located in the activation loop of the JNK protein and activate this kinase in response to environmental stress, pro-inflammatory cytokines or developmental cues. Recent studies, including the analysis with MKK4 and MKK7 knockout mice, have increased our understanding of the physiological roles of JNK signaling in the brain and liver formation, but the precise functions of JNK signaling during early embryogenesis have remained a mystery until relatively recently. Studies employing a range of animal models have now revealed the essential roles of MAPKKs in diverse developmental contexts, including in dorsoventral patterning, convergent extension and somitogenesis. Focusing primarily on extensive work done in zebrafish models, this paper summarizes the functional properties of MKK4 and MKK7 during vertebrate and invertebrate development, and the mechanisms by which these two MAPKKs regulate multiple steps in the formation of the body plan of an organism.

Journal

  • Hikaku seiri seikagaku(Comparative Physiology and Biochemistry)

    Hikaku seiri seikagaku(Comparative Physiology and Biochemistry) 30(2), 59-67, 2013-05-10

    THE JAPANESE SOCIETY FOR COMPARATIVE PHYSIOLOGY AND BIOCHEMISTRY

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Codes

  • NII Article ID (NAID)
    10031170784
  • NII NACSIS-CAT ID (NCID)
    AN10391932
  • Text Lang
    JPN
  • Article Type
    REV
  • ISSN
    09163786
  • NDL Article ID
    024743845
  • NDL Call No.
    Z18-1651
  • Data Source
    CJP  NDL  J-STAGE 
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