スイスの3T3細胞におけるフォスホイノシチダゼCβの核の局所化とシグナル伝達活動
A M Martelli1, R S Gilmour, V Bertagnolo
1Institutes of Human Anatomy, University of Bologna, Italy.
Nature
|July 16, 1992
まとめ
インスリン類似成長因子-1 (IGF-1) は核フォスファチノシチダゼCの活性を誘発し,フォスファチチチルノシトール4,5-ビスホスファート (PtdInsP2) の分解につながります. この核信号伝達経路は,細胞増殖に極めて重要です.
科学分野:
- 細胞生物学 細胞生物学
- 分子シグナリング
- バイオケミストリー バイオケミストリー
背景:
- フォスファチチドリノシトール4,5-ビスホスファート (PtdInsP2) の水解は,プラズマ膜の重要な信号伝達経路である.
- 証拠は,明確な核フォスホイノシチドシグナル伝達システムを示唆しています.
- 核イノシトール脂質レベルは,インスリン類似成長因子-1 (IGF-1) の刺激により低下する.
研究 の 目的:
- 核内のPtdInsP2分解をIGF-1が開始するメカニズムを調査する.
- 核信号伝達に関与する特定のフォスフォニノシチダゼC (PLC) イゾ酵素を特定する.
- IGF-1誘発細胞反応における核PLCの役割を決定する.
主な方法:
- 核フォスホイノシチド合成を in vitroで研究した.
- 核イノシトール脂質とダイアシルグリセロール質量のIGF-1への反応による変化をモニターした.
- 3T3細胞におけるPLC同酵素 (βおよびgamma) の局所化と活性を調べた.
- IGF-1受容体を発現する細胞のミトゲン反応を評価した.
主要な成果:
- 浄化された核はPtdInsP2とフォスファディチルイノシトール4フォスファート (PtdInsP) を合成する.
- IGF-1治療は,核のPtdInsPとPtdInsP2のレベルを一時的に低下させます.
- 核ダイアシルグリセロルが増加し,タンパク質キナーゼCの活性化と転位が先行する.
- 3T3細胞の核には,フォスホイノシチダゼCのβ-同酵素が含まれています.
- IGF-1は,核フォスホイノシチダゼCの活性だけを刺激する.
結論:
- IGF-1によって制御される,固有の核フォスホイノシチドシグナル伝達システムが存在する.
- フォスホイノシチダゼCのβ-同酵素は核内に局限し,IGF-1によって活性化されます.
- 核PLCの活性化は,細胞増殖につながるIGF-1媒介シグナル伝達の重要なステップです.
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