機能的なトロンビン受容体の分子クローニングは,受容体活性化の新しいタンパク質分解機構を明らかにします
T K Vu1, D T Hung, V I Wheaton
1Department of Medicine, University of California, San Francisco 94143-0524.
Cell
|March 22, 1991
まとめ
科学者たちは,トランビン分裂によって活性化される新しいヒトトロンビン受容体を発見しました. この割れは,結合されたリガンドを生成し,血小板と細胞の活性化に不可欠なユニークなシグナル伝達経路を開始します.
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
- Gタンパク質結合受容体とは
背景:
- トロンビンは,血静と血栓形成において重要な役割を果たします.
- トロンビン受容体活性化の正確な分子機構は,完全に解明されていません.
研究 の 目的:
- 機能的なヒトトロンビン受容体を分離し,特徴づけること.
- トロンビン媒介の受容体活性化のメカニズムを解明する.
主な方法:
- Xenopusの卵細胞における直接発現クローニング.
- 受容体のアミノ酸配列の分析.
- 合成ペプチドと変異性受容体を用いた機能分析.
主要な成果:
- ヒトのトロンビン受容体,新しい7つのトランスメンブランドメイン受容体のためのcDNAを分離しました.
- 受容体の細胞外領域内のトロンビン分裂部位を特定しました.
- 分裂したN末端を模倣するペプチドが強力なアゴニストとして作用することを実証した.
- 食べられない受容体変異体は,トロンビンに反応せず,N端ペプチドに反応することを示した.
結論:
- トロンビンは,その受容体をN端延長を割って活性化させ,結合されたリガンドを生成します.
- この新しいメカニズムは,トロンビンのためのユニークなシグナル伝達経路を表しています.
- この発見は,血小板活性化と血管生物学を理解するための意味を持つ.
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