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CREB:カルモジュリン依存キナーゼによってリン酸化されるCa(2+) 調節された転写因子
M Sheng1, M A Thompson, M E Greenberg
1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Science (New York, N.Y.)
|June 7, 1991
まとめ
カルシウムイオン (Ca2+) は,CREB転写因子を活性化するCa2+-カルモジュリン依存タンパク質キナーゼ (CaMキナーゼ) を介して遺伝子誘導を誘発します. セル133におけるCREBのCaMキナーゼによるリン酸化は,核への電気信号伝導に不可欠である.
科学分野:
- 神経科学は神経科学である.
- 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:
- 膜脱極化は,遺伝子誘導を含む細胞反応を誘発する.
- カルシウムイオン (Ca2+) は,これらの反応を媒介する上で重要な役割を果たします.
- アデノシン3',5'-モノフォスファート (cAMP) 応答要素結合タンパク質 (CREB) は,細胞信号伝達に関与する既知の転写因子です.
研究 の 目的:
- 膜脱極化後にCa2+が遺伝子誘導を媒介するメカニズムを調査する.
- この過程におけるCa(2+) -カルモジュリン依存タンパク質キナーゼ (CaMキナーゼ) とCREBの役割を決定する.
主な方法:
- Ca2+シグナル伝達経路を調査した.
- Ca2+調節された転写因子としてのCREBの機能を調べました.
- in vitroおよびin vivoでCaMキナーゼによるCREBのリン酸化を評価した.
- CREBのリン酸化部位を変更するために,部位指向型変異を生成した.
主要な成果:
- CREBはCa2+調節された転写因子として作用する.
- デポラライゼーションで活性化されたCaMキナーゼIとIIは,CREBをリン酸化する.
- CREBのセリン133 (Ser133) は,CaMキナーゼ媒介のリン酸化の主な部位である.
- Ser133の変異は,CA2+に対するCREBの反応を著しく低下させる.
結論:
- CaMキナーゼは,原子核への電気信号の伝達管として機能する.
- CREBはCa2+とcAMPの両方のシグナル伝達経路を統合しています.
- 膜脱極化後のCa2+の流入は,CREBリン酸化による遺伝子発現の重要な調節因子である.
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