変異したATP結合部位を持つp60c-src変異体の酵素的無活性性は,そのカルボキシ末端の調節領域で完全にリン酸化される
Cell
|September 11, 1987
まとめ
細胞のsrcタンパク質 (p60c-src) のチロシン527でのリン酸化は,その活性を調節するために重要である. この研究は,チロシン527のリン酸化がp60c-srcキナーゼ活性とは独立して発生することを示しています.
科学分野:
- 分子生物学は分子生物学である.
- セルラー・シグナリング
- 腫瘍生成 (オンコゲネシス) について
背景:
- 細胞 src タンパク質 (p60c-src) は,非受容体チロシンキナーゼである.
- タイロシン527 (Y527) でのリン酸化は,p60c-src キナーゼ活性とその変換可能性を抑制することが知られている.
- Y527のリン酸化がp60c-src自身のキナーゼ活性に依存するかどうかは不明である.
研究 の 目的:
- p60c-srcにおけるチロシン527のリン酸化が,その固有のタンパク質チロシンキナーゼ活性に依存しているかどうかを調査する.
- p60c-srcの活性を調節するメカニズムと,細胞変容におけるその役割を解明する.
主な方法:
- サイト・ディレクテッド・ミュータゲネシスは,ライシン295をメチオニン (p60c-src(M295) で置き換えて,鶏肉p60c-srcの触媒的に無活性な突然変異を生成するために使用されました.
- 野生型p60c-srcとp60c-src (M295) 変異体の発現とリン酸化パターンは,鶏の細胞と酵母で分析されました.
主要な成果:
- p60c-src(M295) 変異体は,鶏の細胞と酵母の両方で検出可能なタンパク質チロシンキナーゼ活性を示さなかった.
- 鶏の細胞におけるチロシンおよびセリン残留物に対するp60c-src ((M295) のリン酸化は,野生型のp60c-src.と比べられる.
- しかし,p60c-src(M295) は酵母で発現するとチロシンリン酸化に失敗した.
結論:
- ティロシン527によるp60c-srcのリン酸化は,p60c-src自身のキナーゼ活性から独立している.
- 鶏の細胞に存在するが,酵母に存在しないトランス作用タンパク質キナーゼは,チロシン527をリン酸化する責任を負う.
- これらの発見は,p60c-srcと異なるキナーゼがY527のリン酸化を媒介し,SRCキナーゼの調節に関する洞察を提供することを示唆しています.
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