キナーゼ挿入領域のPDGF受容体の自己リン酸化は,細胞タンパク質との相互作用を調節する
1Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Cell
|September 22, 1989
まとめ
血小板由来成長因子受容体 (PDGF-R) の自己リン酸化部位が特定されました. キナーゼ挿入領域のリン酸化により,PDGF-Rがフォスファディチルイノシトール3キナーゼと結合し,信号伝導に影響を与えます.
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
背景:
- 血小板由来成長因子受容体 (PDGF-R) は,細胞過程の重要な調節因子である.
- 受容体チロシンキナーゼの自己リン酸化は,信号伝導に極めて重要です.
研究 の 目的:
- ヒトのPDGF-RβサブユニットにおけるPDGFに依存した自己リン酸化部位を特定し,特徴づけること.
- PDGF-Rのシグナル伝達とタンパク質の相互作用におけるこれらの部位の役割を調査する.
主な方法:
- PDGF-Rβサブユニットのサイト指向型変異.
- PDGF-RをPDGFで治療した細胞から免疫圧縮する.
- 関連するフォスファティディル・イノシトール3キナーゼ活性に関する測定.
主要な成果:
- 2つの主要な自己リン酸化部位が特定されました:Tyr-857 (主要部位) とTyr-751 (キナーゼ挿入部位).
- Tyr-751または触媒ドメインの変異により,PDGF-Rとフォスファディチルイノシトール3-キナーゼおよび他のタンパク質との関連が廃止されました.
- キナーゼ挿入領域における自己リン酸化は,シグナリング分子の徴集に不可欠である.
結論:
- 特にTyr-751でのPDGF-Rオートフォスフォリレーションは,下流シグナルイベントの開始に不可欠です.
- このプロセスは,Phosphatidylinositol 3-キナーゼおよび他のタンパク質の募集を含み,PDGF主導の細胞応答を媒介する.
- オートフォスフォリレーションはPDGF-R信号伝達経路において新しい役割を果たします.
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