rasは,3つの信号変換タンパク質キナーゼの神経成長因子受容体調節を媒介する:MAPキナーゼ,Raf-1,RSK
K W Wood1, C Sarnecki, T M Roberts
1Program in Cell and Developmental Biology, Harvard University, Boston, Massachusetts.
Cell
|March 20, 1992
まとめ
Rasタンパク質 (p21c-ras) は細胞成長に不可欠ですが,そのシグナル伝達経路は不明でした. この研究は,RASが神経成長因子とタンパク質キナーゼCを媒介することを示し,MAPキナーゼ,RSK,Raf-1に対する効果を示している.
科学分野:
- セルラー・シグナリング
- 分子生物学は分子生物学である.
- 腫瘍生成 (オンコゲネシス) について
背景:
- p21c-rasはチロシンキナーゼによって刺激される細胞の成長と分化に不可欠です.
- p21c-rasが利用する特定のシグナル伝達経路は,依然としてほとんど不明です.
- これらの経路を理解することは,成長因子に対する細胞の反応を解読する鍵です.
研究 の 目的:
- p21c-ras.によって伝播される下流の信号経路を解明する.
- MAPキナーゼ,RSK,Raf-1の調節におけるrasの役割を調査する.
- 成長因子とホルボールエステルがこれらのシグナル伝達分子を ras.経由でどのように活性化するかを決定する.
主な方法:
- PC12細胞におけるras (c-Ha-ras(Asn-17) の支配的阻害性変異体を利用した.
- MAPキナーゼ (ERKファミリー),RSK,Raf-1の活性化を評価した.
- 主要な阻害性突然変異体を発現する細胞のシグナル伝達と,活性化されたRAS腫瘍遺伝子を発現する細胞のシグナル伝達を比較した.
主要な成果:
- c-Ha-ras ((Asn-17) の発現は,MAPキナーゼ,RSK,Raf-1キナーゼの抑制された成長因子およびホルボールエステル誘発の活性化を引き起こします.
- 逆に,活性化されたras腫瘍遺伝子の発現は,これらのシグナルイベントを刺激するのに十分であった.
- これらの発見は,これらのシグナリングカスケードにおけるRASを中心的な媒介者として特定しています.
結論:
- ラスタンパク質は,神経成長因子受容体とタンパク質キナーゼCからのシグナル伝達の重要な媒介者である.
- RasはMAPキナーゼ,RSK,Raf-1の活性化に影響する.
- この研究は,人種間介的細胞成長と分化経路のより明確な理解を提供します.
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