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Cdk5によるDARPP-32のリン酸化は,ニューロンにおけるドーパミンシグナル伝達を調節する

J A Bibb¹, G L Snyder, A Nishi

¹Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA.

|December 22, 1999

まとめ

DARPP-32は二重機能の分子として作用する. トレオニン34のリン酸化により,フォスファターゼ阻害体となり,トレオニン75のリン酸化により,キナーゼ阻害体となり,細胞信号伝達を調節する.

科学分野:

セルラー・シグナリング
分子生物学は分子生物学である.
神経科学は神経科学である.

背景:

細胞生理学は信号伝達経路に依存しています.
タンパク質キナーゼとフォスファタゼは,細胞のバランスを維持します.
DARPP-32は,ドーパミンとcAMPのシグナル伝達における重要な調節体である.

研究の目的:

信号伝達におけるDARPP-32の二重の役割を調査する.
微分リン酸化がDARPP-32機能にどのように影響するかを理解するために.
タンパク質キナーゼとフォスファタゼの活動を制御するメカニズムを解明する.

主な方法:

タンパク質キナーゼA (PKA) とサイクリン依存キナーゼ5 (Cdk5) を用いた実験室内リン酸化アッセイ.
完ぺきな脳細胞とストライアタルスライスに関する研究.
Cdk5固有の阻害剤と遺伝子組み換えマウスを用いた.

主要な成果:

PKAによるスレオニン34におけるDARPP-32のリン酸化により,タンパク質フォスファターゼ1阻害剤が作られる.
Cdk5によるセロニン75でのリン酸化により,PKA阻害剤が生成されます.
Cdk5の阻害またはフォスフォ-スロの減少 75 DARPP-32 ドーパミン誘発のPKA基板リン酸化とカルシウム電流の増加.

結論:

DARPP-32は双機能信号伝達タンパク質である.
異なった部位での異なったリン酸化が,キナーゼやリン酸塩酵素に対する抑制作用を決定する.
このメカニズムは,細胞信号伝達経路の複雑な制御を提供します.

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