ミオシン・ライトチェーンキナーゼの抑制は,p21活性化キナーゼによって行われる
L C Sanders1, F Matsumura, G M Bokoch
1Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
まとめ
p21活性化キナーゼ (PAKs) は,ミオシン軽鎖キナーゼ (MLCK) を標的にし,その活性とミオシン軽鎖リン酸化を低下させます. このメカニズムは,細胞骨格動態と細胞拡散を調節する.
科学分野:
- 細胞生物学 細胞生物学
- 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:
- p21活性化キナーゼ (PAKs) は,Rho GTPasesによって影響される細胞骨格動態の主要な調節因子です.
- 細胞骨格動態は,ミオシン・ライトチェーン・キナーゼ (MLCK) 媒介によるミオシン・ライトチェーン・キナーゼ (MLCK) 媒介のリン酸化によって調節されるアクチンとミオシンIIの相互作用に依存する.
研究 の 目的:
- ミオシンライトチェーンキナーゼ (MLCK) の活性を調節するp21活性化キナーゼ1 (PAK1) の役割を調査する.
- PAKsがMLCKのリン酸化によって細胞骨格の動態を調節するかどうかを決定する.
主な方法:
- ベビーハムスターの腎臓-21およびHeLa細胞における構成的に活性なPAK1の発現.
- MLCKの活性とMLCのリン酸化レベルを測定するためのアッセイ.
- 細胞骨格動態の指標としての細胞拡散の評価.
主要な成果:
- PAK1はMLCKをリン酸化し,MLCKの活性が低下することが判明しました.
- 活性PAK1.1.を発現する細胞で,MLCKの活性低下とMLCのリン酸化が観察されました.
- 細胞拡散の阻害は,PAK1発現が活発な細胞で観察されました.
結論:
- ミオシン軽鎖キナーゼ (MLCK) は,p21活性化キナーゼ (PAKs) の直接標的である.
- PAKは,MLCKの活性およびその後のMLCのリン酸化を阻害し,細胞の拡散に影響を与えることによって,細胞骨格動態を調節する.
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