TORキナーゼドメインは2つの異なる機能のために必要であり,そのうちの1つだけがラパミシンによって抑制されます
X F Zheng1, D Florentino, J Chen
1Howard Hughes Medical Institute Department of Chemistry, Harvard University Cambridge, Massachusetts 02138, USA.
Cell
|July 14, 1995
まとめ
TOR1およびTOR2タンパク質を含むラパミシン敏感経路は,細胞サイクル進行を調節する. キナーゼ活性がG1機能に不可欠であり,ラパミシンは選択的にこのプロセスを阻害する.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- ラパミシンに敏感な経路は,細胞サイクル機構にミトゲン信号を伝達する上で,特にG1相進行において極めて重要です.
- イーストにおける遺伝学的研究により,この経路における重要な遺伝子としてTOR1とTOR2が特定され,これは新しいフォスファティディル・イノシトール・キナーゼであると仮定されている.
研究 の 目的:
- TOR1およびTOR2タンパク質におけるキナーゼドメインの機能的要件を調査し,G1細胞サイクル進行におけるそれらの役割について調べる.
- FKBP12-ラパミシンがTORタンパク質の機能,特にG1相および重要な細胞プロセスに影響を与えるメカニズムを解明する.
主な方法:
- TOR1およびTOR2遺伝子に変異がある酵母菌株の遺伝子分析.
- ラパミシン治療を含む様々な条件下での細胞サイクル進行 (G1) と細胞成長の評価.
- TORタンパク質のキナーゼとFKBP12-ラパミシン結合ドメインの機能的特徴.
主要な成果:
- 完ぺきなキナーゼドメインは,TOR1とTOR2の両方のタンパク質のG1細胞サイクル機能に不可欠です.
- 変異したTOR1タンパク質の過剰発現 (FKBP12-ラパミシン結合ドメインに影響する) は,酵母細胞の成長を抑制した.
- TOR2の重要な機能には,無傷のキナーゼドメインが必要ですが,この機能はラパミシンに敏感ではありません.
- 両方のTORタンパク質のG1機能はラパミシンに敏感であるが,TOR2の基本的な機能はそうではない.
結論:
- TORタンパク質のキナーゼ活動は,それらのG1細胞サイクル機能にとって不可欠である.
- FKBP12-ラパミシンは,TORキナーゼの活性を広く抑制することはありませんが,効果因子相互作用またはリン酸化に選択的に干渉する可能性があります.
- この選択的干渉は,細胞サイクル制御と重要な細胞プロセスにおけるTORタンパク質の微妙な規制メカニズムを示唆しています.
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