p70/p85 S6キナーゼの活性化は,p21rasから独立した経路によって行われる
X F Ming1, B M Burgering, S Wennström
1Friedrich Miescher Institute, Basel, Switzerland.
Nature
|September 29, 1994
まとめ
細胞成長に不可欠なp70s6k/p85s6kシグナル伝達経路は,p21ras.と独立しています. この経路は,受容体レベルでp21ras経路から逸脱し,オートフォスフォリレーションによって開始されます.
科学分野:
- 細胞の信号伝達経路は,
- 分子生物学は分子生物学である.
- キナーゼシグナル伝達
背景:
- p70s6kとp85s6kは,ミトゲネシスに不可欠なキナーゼのアイソフォームです.
- その活性化には,複雑なリン酸化と,p42mapk/p44mapk.から異なるシグナル伝達経路が必要です.
- p42mapk/p44mapkの活性化は,Sos,p21ras,p74raf,およびp47mekの下流にある.
研究 の 目的:
- p70s6k/p85s6k信号経路がp21ras経路から離れているかどうかを調べる.
- この2つのシグナリングカスケードの分岐点を決定する.
主な方法:
- p74rafとp21rasの突然変異を用いて,p44mapkとp70s6kの活性化への影響を評価した.
- 改変されたヒト血小板由来成長因子受容体 (キナーゼ挿入ドメインが欠けている) を発現する細胞のシグナリングを分析する.
- 受容体領域内の重要な自己リン酸化部位を特定する.
主要な成果:
- p74rafとp21rasの変異体はp44mapkの活性化を抑制したが,p70s6kの活性化を抑制しなかった.
- 成長因子p21rasの活性化が観察されたが,PDGF受容体が改変された細胞ではp70s6k/p85s6kは観察されなかった.
- タイロシン残基751は,p70s6k/p85s6k活性化のための重要な自己リン酸化部位として特定されました.
結論:
- p70s6k/p85s6kシグナル伝達経路は,p21ras.kから独立しています.
- p70s6k/p85s6kとp21ras経路の分岐点は,受容体レベルにある.
- p70s6k/p85s6k経路の開始は,特定の部位 (Tyr751) での自己リン酸化によって起こります.
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