核酸交換因子Sosの膜ターゲティングは,Ras信号経路の活性化に十分である
A Aronheim1, D Engelberg, N Li
1Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636.
Cell
|September 23, 1994
まとめ
プラズマ膜にSOSタンパク質を標的にすることは,Ras信号伝達経路を活性化するための鍵です. 特にRasの近くのSosの膜採用は,腫瘍性変異と経路刺激を誘発する.
科学分野:
- 細胞生物学 細胞生物学
- 分子シグナル伝達です.
- 腫瘍生成 (オンコゲネシス) について
背景:
- 成長因子受容体の活性化は,チロシン自己リン酸化を含むシグナリングカスケードを開始します.
- Grb2のようなSH2ドメインを含むタンパク質は,活性化された受容体に採用されます.
- Grb2媒介によるRas経路のSos活性化の正確なメカニズムは不明である.
研究 の 目的:
- ソス媒介のRas経路の活性化における膜リクルートメントの役割を調査する.
- Sosのプラズマ膜ターゲティングがRas経路を活性化するのに十分かどうかを判断する.
- SosがRas信号を活性化するメカニズムを解明する.
主な方法:
- プラズマ膜標的化のためのミリスチル化またはファルネシル化信号を持つエンジニアリングされたSOSタンパク質誘導体.
- ERKとAP-1の活動を含む Ras信号経路の活性化を評価しました.
- 哺乳類の細胞と酵母モデルの両方を利用して,SOSの機能を研究しました.
- C端末領域が欠けている生成ソス・デリバティブ.
主要な成果:
- Sosのミリスチル化またはファルネシル化により,それがプラズマ膜に成功し,Ras経路を刺激し,腫瘍性変異につながった.
- 非機能的な脂質改変配列は,経路を活性化しませんでした.
- 膜を標的としたSOSは,酵母におけるRasシグナリングを活性化させた.
- C端末領域を欠いたSOS誘導体は,両方の細胞タイプにおいて,著しく活性化を示した.
結論:
- Sosのプラズマ膜ターゲティング,特にRasの近くに,Ras経路の活性化の主なドライバーです.
- Sos C端末領域による抑制の緩和は,二次的な活性化メカニズムを表す可能性があります.
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