Eps8タンパク質は,Rac経由でEGF受容体シグナル伝達とRab5経由で取引を調整する
L Lanzetti1, V Rybin, M G Malabarba
1Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Nature
|December 1, 2000
まとめ
タンパク質Eps8は,RacとRab5GTPasesと相互作用することによって,表皮成長因子受容体 (EGFR) 信号伝達とトラフィッキングをリンクします. この統合はEGFRの内部化とRacの信号伝達経路を調節する.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- シグナルトランスデュークション
背景:
- 皮膚表皮成長因子受容体 (EGFR) 信号伝達経路は,細胞の成長と分化に不可欠です.
- EGFRの密輸は,受容体の内部化を伴うもので,信号の終止と調節に不可欠です.
- EGFRシグナル伝達とトラフィックの相互作用,特にRhoとRabファミリーのGTPaseが関与する相互作用は,まだ十分に理解されていません.
研究 の 目的:
- EGFRシグナル伝達と取引を結びつける分子メカニズムを解明する.
- RhoとRab GTPasesによって媒介される経路を統合するタンパク質を特定する.
- この統合ネットワークにおけるEps8タンパク質の役割を調査する.
主な方法:
- コイムノプレシピテーションは,タンパク質複合体を特定するための測定法です.
- GTPase活性化タンパク質 (GAP) アッセイは,酵素活性を決定する.
- タンパク質レベルと活性化状態を評価するためのウェスタン・ブロッティング.
- コンフォカル顕微鏡でEGFRの密輸と局所化を視覚化します.
主要な成果:
- Eps8はEGFRシグナル伝達 (Rac経由) と人身売買 (Rab5経由) を結びつける支架として機能する.
- Eps8はSos1とアダプタタンパク質E3b1と相互作用して,Rac.を活性化します.
- また,Eps8は,EGFRによって調節されるRab5 GTPase活性化タンパク質 (GAP) であるRN-treと相互作用します.
- RN-treがEps8に結合すると,EGFRの内部化を阻害し,Racのシグナリングを弱める.
結論:
- Eps8はEGFRのシグナル伝達とトラフィックの経路の重要な分子インテグレーターです.
- Eps8のE3b1/Sos1またはRN-treとの相互作用は,Racの活性化またはRab5媒介の取引における機能を決定する.
- このEps8の二重な役割は,EGFRシグナル伝達とエンドサイトーシスの調整のためのメカニズムを提供します.
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