新型WDリピートタンパク質であるFANは,p55 TNF受容体を中性スフィンゴミエリンゼと結合させます
S Adam-Klages1, D Adam, K Wiegmann
1Institut für Immunologie, Christian-Albrechts-Universität Kiel, Federal Republic of Germany.
Cell
|September 20, 1996
まとめ
研究者らは,腫瘍死滅因子受容体 (TNF-R55) と結合する新しいタンパク質であるFANを特定した. FANは,中性スフィンゴミエリンゼ (N-SMase) を介してセラミド生成を調節し,TNFシグナル伝達経路の重要なステップです.
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:
- 55 kDaの腫瘍死滅因子受容体 (TNF-R55) によって開始される細胞内信号伝達は,その細胞プラズマ領域と相互作用するタンパク質中間物質を含む.
- TNF-R55の細胞質領域内の特定の9アミノ酸モチーフは,中性スフィンゴミエリンゼ (N-SMase) の活性化に不可欠です.
研究 の 目的:
- TNF-R55シグナル伝達に関与する新しいタンパク質中間体を特定する.
- N-SMaseの活性化およびその後のシグナリングイベントにおけるこれらの中間物質の役割を明らかにする.
主な方法:
- 相互作用するタンパク質をスクリーニングするために,酵母相互作用トラップシステムを利用しました.
- 結合モチーフを特定するためにペプチドスキャンライブラリを使用しました.
- TNF治療を受けた細胞におけるN-SMase活性に対するFANタンパク質発現 (全長および変異) の影響を調査した.
主要な成果:
- FANと呼ばれる新しいWD-リピートタンパク質を特定し,TNF-R55.5の9つのアミノ酸モチーフに特異的に結合した.
- 全長FANの過剰発現は,TNFで刺激された細胞におけるN-SMaseの活性を高めました.
- 断片化されたFAN変異体は,N-SMaseの活性を抑制する,支配的な負の効果を示した.
結論:
- FANは,TNF-R55媒介の細胞内信号伝達の重要な調節体として作用する.
- TNF-R55とのFANの相互作用は,N-SMaseの活性を調節し,セラミド生成とTNFシグナル伝達経路に影響を与えます.
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