リンガンド誘発の内部化とカルシウム調節に必要なドメインからの表皮成長因子受容体の機能的独立性
W S Chen1, C S Lazar, K A Lund
1School of Medicine, University of California, San Diego, La Jolla 92093.
Cell
|October 6, 1989
まとめ
研究者らは,表皮成長因子 (EGF) 受容体C端の特定の配列を特定し,受容体内化,下調調節,および退化に不可欠である. この発見は,EGFのシグナリングがどのように規制され,終了されるかを明確にします.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- 受容体生物学 受容体生物学
背景:
- 皮膚表皮成長因子 (EGF) 受容体は,細胞の成長と増殖の主要な調節体である.
- 内部化と分解を含むEGF受容体調節のメカニズムを理解することは,細胞反応を理解するために不可欠です.
- これらのプロセスに関わる正確なシーケンスとドメインは,完全に解明されていません.
研究 の 目的:
- EGF受容体内にあるEGF受容体C端の特定の配列を特定し,EGFに依存する受容体内化に責任を負う.
- この配列が受容体のダウンレギュレーション,分解,およびダウンストリームシグナル伝達における役割を調査する.
- キナーゼ活性,内部化,およびミトゲンシグナル伝達との関係を解明する.
主な方法:
- EGF受容体内の重要なアミノ酸配列を特定するためのサイト指向型変異.
- 細胞ベースの測定は,受容体の内部化,分解,およびカルシウムシグナル伝達を測定する.
- EGF刺激に対する遺伝子転写と形態学的変容の分析.
主要な成果:
- タイロシンキナーゼドメインの遠隔境界と明確なC'-端末配列は,EGF受容体の内部化に不可欠である.
- 高親和性エンドサイトーシスとリガンド刺激によるカルシウム増加には,18アミノ酸の負の電荷を持つ領域が必要である.
- キナーゼ活性だが,内部化欠陥のある受容体は,遺伝子転写と細胞成長のシグナルを送り続けることができる.
結論:
- EGF受容体のリガンド誘発的内部化は,特定のC'-端末配列によって媒介され,ミトゲンシグナル伝達を終了するのに役立ちます.
- EGF受容体のダウンレギュレーションと分解は,持続的なシグナリングを防ぐために非常に重要です.
- ミトゲン反応は主に内在のタンパク質チロシンキナーゼ活性によって引き起こされ,内在化が負のフィードバックメカニズムとして作用します.
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