ダイメリゼーションは,受容体のようなタンパク質-チロシン・フォスファタゼ-アルファの活動を抑制する
1Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. gjiang@aim.salk.edu
Nature
|October 19, 1999
まとめ
ダイメリゼーションは,受容体型のタンパク質チロシン・フォスファタゼα (RPTPalpha) の活性 in vivo を否定的に調節する. この調節はステレオ化学的に結晶構造と一致しており,細胞の成長と分化を制御するメカニズムを示唆しています.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- バイオケミストリー バイオケミストリー
背景:
- タンパク質チロシンファスファターゼ (PTPs) は,細胞のプロセスに不可欠です.
- 受容体型のPTP (RPTP) 調節は完全に理解されていません.
- 結晶構造は,RPTPalpha二極化が活性を抑制する可能性があることを示唆しています.
研究 の 目的:
- ダイメリゼーションによる全長RPTPalpha活性のインビボ調節を調査する.
- ダイメリゼーションがRPTPalpha機能に悪影響を及ぼすかどうかを判断する.
- RPTPalphaの二酸化媒介阻害の構造的基礎を確認するために.
主な方法:
- システイン変異体を使用して,安定した二硫化物結合RPTPalphaホモダイマーを生成した.
- RPTPalpha-nullマウスの胚細胞で表現された野生型および変異RPTPalpha.
- 評価されたc-Src Tyr 529の脱酸化と活性.
主要な成果:
- ダイメリゼーションは,RPTPalphaの全長活性 in vivoを抑制することが示されました.
- 特定のシステイン変異 (Phe135Cys,Thr141Cys) は,二酸化を可能にし,c-Src活性を増大させた.
- 阻害ケイジ (Pro210/211 から Leu) を変異させることで,二分化欠陥のある変異体におけるc-Src活性化が回復した.
結論:
- RPTPalphaの活動は, in vivo の二分化によって負の調節が可能である.
- 抑制メカニズムは,RPTPalpha.の構造データと一致しています.
- ディメリゼーションは,細胞シグナル伝達におけるRPTPアルファの潜在的な規制メカニズムを提供します.
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