外部から添加された酸性線維芽細胞成長因子による二重モードの信号伝導
A Wiedłocha1, P O Falnes, I H Madshus
1Institute for Cancer Research, Norwegian Radium Hospital, Montebello, Oslo.
Cell
|March 25, 1994
まとめ
酸性線維細胞成長因子 (aFGF) 融合タンパク質は,aFGF受容体が欠けている細胞でDNA合成を刺激しました. 細胞核への侵入は,aFGFがDNA合成を促進するために決定的であり,二重信号伝達経路を示しています.
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.
- バイオケミストリー バイオケミストリー
背景:
- 酸性線維細胞成長因子 (aFGF) は,細胞増殖と生存の重要な調節因子である.
- ディフテリア毒素 (Diphtheria toxin,DT) は強力な毒素で,受容体媒介性内分泌作用 (receptor-mediated endocytosis) を通して細胞に入り込む.
- 成長因子のシグナル伝達経路を理解することは,標的治療の開発に不可欠です.
研究 の 目的:
- aFGFのシグナル伝達機構,特に細胞表面受容体と細胞内輸送の役割を調査する.
- aFGFとDTの融合タンパク質が信号伝達のための細胞表面受容体要件を回避できるかどうかを判断する.
- 核転位がFGF媒介のDNA合成に与える影響を明らかにする.
主な方法:
- aFGF-ディフテリア毒素融合タンパク質の構築と応用.
- 毒素耐性およびaFGF受容体欠乏細胞系 (NIH 3T3) を利用する.
- aFGFと融合タンパク質への反応としてDNA合成とチロシンリン酸化を評価する.
主要な成果:
- aFGF-DT融合タンパク質は,機能的なaFGF受容体を持たないが,DT受容体を持つ細胞におけるDNA合成を刺激した.
- NIH 3T3細胞 (DT受容体がないが,aFGF受容体を持つ) では,aFGFと融合タンパク質の両方がチロシンリン酸化を誘導した.
- 核に転移し,NIH 3T3細胞でDNA合成を刺激したのは,融合タンパク質ではなく,ネイティブのaFGFのみです.
結論:
- aFGFによる細胞信号伝達は,細胞表面受容体媒介経路と細胞内輸送の両方を含む.
- aFGFの核入りは,DNA合成を刺激するために不可欠です.
- この研究は,成長因子シグナル伝達と細胞応答を制御する複雑なメカニズムを強調しています.
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