細胞核へのシリア神経栄養因子の信号伝達経路の特徴化

A Bonni¹, D A Frank, C Schindler

¹Program in Neuroscience, Harvard Medical School, Boston, MA 02115.

Science (New York, N.Y.)

|December 3, 1993

まとめ

研究者らは,シリア神経栄養因子 (CNTF) 受容体と遺伝子転写を結びつけるシグナル伝達経路を特定した. この経路は,p91タンパク質の活性化と核転位を含み,CNTF反応性遺伝子発現に不可欠です.

科学分野:

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.
細胞シグナル伝達細胞信号伝達

背景:

神経栄養素因子 (CNTF) は,神経細胞の生存と分化に役割を果たします.
CNTFが核に信号を送る分子メカニズムを理解することは,その生物学的機能を明らかにするために極めて重要です.

研究の目的:

CNTF受容体と遺伝子転写の誘導を結びつける信号伝達経路の構成要素を特定する.
CNTF媒介による転写調節におけるp91を含む特定のタンパク質の役割を明らかにする.

主な方法:

タンパク質の活性化を検出するためのチロシンリン酸化測定法.
サブセルラー分断と核転位の研究.
タンパク質とDNAの相互作用を評価するためのDNA結合測定法.
レポーター遺伝子解析は,転写活動を測定する.

主要な成果:

CNTFの刺激により,p91および関連するタンパク質のチロシンリン酸化が発生した.
リン酸化p91および関連するタンパク質が核に転位した.
これらのタンパク質は,CNTF反応性遺伝子プロモーターの特定のDNA配列に結合する.
このDNA配列は,レポーター遺伝子とリンクされたとき,CNTFへの転写応答を媒介した.

結論:

CNTF受容体と転写誘導を結びつけるシグナル伝達経路が特定されました.
p91タンパク質および関連する要因は,CNTFの転写効果の主要な媒介者である.
インターフェロンシグナル伝達に関与する経路は,特定の神経栄養素因子に対する反応を広めるために利用されることもあります.

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