LAT:ZAP-70のチロシンキナーゼ基板で,T細胞受容体を細胞活性化に結びつける
W Zhang1, J Sloan-Lancaster, J Kitchen
1Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
Cell
|March 7, 1998
まとめ
研究者らは,T細胞受容体シグナル伝達に不可欠な新しいタンパク質,LAT (T細胞の活性化のためのリンカー) を特定しました. 特定のキナーゼによるLATのリン酸化は,T細胞活性化に不可欠な他の分子を募集します.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 細胞シグナリング 細胞シグナリング
背景:
- T細胞受容体 (TCR) 媒介のシグナル伝達は,適応免疫に不可欠である.
- TCR経路の重要なシグナリングコンポーネントは,未だに捉え難いままです.
- 以前の研究では,Grb2,フォスフォリファーゼC-ガンマ1およびPI3K p85サブユニットに関連した36-38 kDaのタンパク質を特定しました.
研究 の 目的:
- TCRシグナル伝達に関与する新しいタンパク質を特定し,特徴づけること.
- このタンパク質がT細胞活性化における役割を明らかにする.
主な方法:
- 36~38 kDa のタンパク質のためのcDNAのクローン化.
- タンパク質の構造と機能を予測するためのアミノ酸配列分析.
- ZAP-70/Sykタンパク質チロシンキナーゼを用いたインビトロリン酸化アッセイ.
- T細胞における野生型および変異型タンパク質の過剰発現に関する研究.
主要な成果:
- 新型タンパク質は,多重なリン酸化部位を持つ高度にチロシン・リン酸化された統合膜タンパク質です.
- ZAP-70/Sykによるリン酸化は,下流のシグナリング分子の採用につながります.
- 重要なチロシン残留物を欠く変異LATの過剰発現は,T細胞の活性化を阻害する.
- このタンパク質はLAT (T細胞の活性化のためのリンカー) と命名された.
結論:
- LATはTCR信号複合体の重要な構成要素である.
- LATはアダプタータンパク質として機能し,T細胞活性化に不可欠なシグナル伝達分子の募集を媒介する.
- LATは,T細胞の反応を理解し,潜在的に調節するための重要なターゲットです.
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