c-Junキナーゼのストレス活性化タンパク質キナーゼサブファミリーである
J M Kyriakis1, P Banerjee, E Nikolakaki
1Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, Charlestown 02129.
Nature
|May 12, 1994
まとめ
ストレス活性化タンパク質キナーゼ (SAPKs) は,MAPキナーゼの新種である. これらのキナーゼは,細胞のストレスと腫瘍死滅因子-αによって活性化され,c-Junの活動を調節します.
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.
- バイオケミストリー バイオケミストリー
背景:
- ミトゲン活性化タンパク質 (MAP) キナーゼErk-1とErk-2は,チロシンとスレオニン酸化によって活性化されるプロリン誘導キナーゼです.
- キナーゼp54は,Erks-1/2に似ているが,プロリン誘導であり,活性化にはTyrとSer/Thrのリン酸化が必要である.
- p54は固有の基板特異性を示し,c-Junトランザクティベーションドメインをpp90rsk.sk.より活発にリン酸化する.
研究 の 目的:
- キナーゼp54とそのサブファミリーである細胞外調節キナーゼを特徴づけるために.
- p54.4. に関する活性化メカニズムとシグナル伝達経路を調査する.
- 細胞のストレス反応とTNF-αシグナル伝達におけるp54の役割を確立する.
主な方法:
- p54の分子クローニング.
- キナーゼ活性と基板特異性の分析.
- ミトゲン,ホルボールエステル,細胞ストレス,腫瘍死滅因子 (TNF) -alpha.
主要な成果:
- 分子クローニングにより,p54は,ストレス活性化タンパク質キナーゼ (SAPKs) と呼ばれる細胞外調節キナーゼのユニークなサブファミリーに属していることが明らかになった.
- SAPKはErks-1/2と40~45%同一であるが,ミトゲンやホルボールのエステルによって活性化が弱くなっている.
- SAPKsは,細胞ストレスとTNF-αによって活性化される主要なc-Jun N-末端キナーゼであり,スフィンゴミエリンゼによっても活性化されます.
結論:
- SAPKsは,TNF-αと細胞ストレスによって活性化される新しいシグナル伝達経路を定義します.
- この経路は,スフィンゴミエリンベースのセカンドメッセンジャーによって開始されることがあります.
- SAPKsは,ストレスへの反応としてc-JunとTNF-alpha.の活動を調節する上で重要な役割を果たします.
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