成長因子刺激と腫瘍学的変異における共通要素:85 kdのフォスフォタンパク質とフォスファディチルニノシトールキナーゼ活性
Cell
|September 25, 1987
まとめ
血小板派生成長因子 (PDGF) とポリオマの中央T抗原 (MTAg) は,85 kdのタンパク質のチロシンリン酸化を誘発し,フォスファディチル・イノシトール (PI) キナーゼ活性を増大させます. このフォスフォタンパク質はチロシンキナーゼの基板である.
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:
- タイロシンリン酸化は,細胞の信号伝達経路において重要な役割を果たします.
- 血小板由来成長因子 (PDGF) は,細胞の成長と分化に関与する強力なミトゲンです.
- ポリオーマの中央T抗原 (MTAg) は,細胞変容を誘発できるウイルス性オンコタンパク質です.
研究 の 目的:
- PDGF刺激とMTAg変換に対する細胞応答におけるチロシンリン酸化の役割を調査する.
- これらの細胞イベントに関連するタンパク質と酵素活動を特定する.
主な方法:
- イムノプレシピテーションのために,フォスフォチロジン (P-tyr) に対する抗体を利用した.
- 3T3細胞におけるタンパク質リン酸化とフォスファディチルイノシトール (PI) キナーゼ活性を調べた.
- 分析した細胞はPDGFによって刺激され,MTAg,v-fms,v-sis,SV40 T抗原によって変換された.
主要な成果:
- 85kdのタンパク質の急速なチロシンリン酸化と,PDGF刺激やMTAg変換時にPIキナーゼ活性の増加が観察されました.
- 85kdのフォスフォタンパク質とPIキナーゼ活性も,v-fmsとv-sisによって変換された細胞では上昇したが,SV40T抗原では上昇しなかった.
- 浄化中にチロシンリン酸化85kdタンパク質とPIキナーゼ活性との間に強い相関が認められた.
結論:
- フォスファディチリノシトール (PI) キナーゼである可能性が高い85 kdのフォスフォプロテインは,PDGF受容体とMTAg/pp60c-srcチロシンキナーゼ活動のための重要な基板です.
- これらの発見は,成長因子とウイルスのオンコタンパク質への反応としてチロシンリン酸化とPIキナーゼ活性化を含むシグナル伝達経路を明らかにしています.
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