活性化されたB細胞におけるヴァー・プロトオンコゲン産物のチロシンリン酸化
1Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Science (New York, N.Y.)
|May 22, 1992
まとめ
B型リンパ球の活性化には,p95vavのチロシンリン酸化が含まれる.p95vavは,vAV原発がん遺伝子に関連したタンパク質である. このリン酸化とVap-1との関連は急速であり, vav vav を示唆しています.
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.
- 細胞シグナル伝達 細胞信号伝達
背景:
- B型リンパ球は,免疫グロブリンM (IgM) 抗原受容体を通して活性化されます.
- この活性化は,タンパク質チロシンリン酸化を含む細胞内シグナリングカスケードを誘発する.
- vavプロトオンコゲン産物であるp95vavは,これらのシグナル伝達経路に関与する重要なタンパク質である.
研究 の 目的:
- IgM受容体の関与によるBリンパ球の活性化におけるp95vavの役割を調査する.
- p95vavチロシンリン酸化の動力学と依存性を決定する.
- B細胞の活性化中にp95vavが他のシグナル伝達分子と相互作用することを調査する.
主な方法:
- 免疫グロブリンM (IgM) がBリンパ球に交差する.
- 特定の抗体を用いてタンパク質チロシンリン酸化の分析.
- 共同免疫プレシピテーションによるタンパク質-タンパク質相互作用の評価.
- タンパク質相互作用におけるSrcホモロジー2 (SH2) ドメインの役割を調査する.
主要な成果:
- p95vavのチロシンリン酸化は,IgMクロスリンク後,迅速に (数秒以内に) 発生する.
- p95vavのリン酸化は,タンパク質キナーゼCの活性化,Gタンパク質のシグナル伝達,およびカルシウム動員から独立しています.
- p95vavは,約5秒以内に,70 kDaのチロシン・リン酸化タンパク質であるVap-1と急速に結合します.
- この関連は一時的で,約60秒持続し,p95vav.のSH2ドメインによって媒介されます.
結論:
- vavプロトオンコゲン産物であるp95vavは,Bリンパ球抗原受容体シグナル伝達における早期応答である.
- p95vavのリン酸化とVap-1との相互作用は,B細胞活性化における重要な早期イベントである.
- これらの発見は,抗原誘発Bリンパ球活性化を媒介するvAV原発がん遺伝子の重要な役割を強調しています.
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