STATタンパク質によるインターフェロンアルファおよびインターフェロンベータ刺激遺伝子発現におけるMAPキナーゼ (ERK2) 活性に対する要求

M David¹, E Petricoin, C Benjamin

¹Division of Cytokine Biology, Center for Biologics Evaluation and Research, Bethesda, MD 20892, USA.

Science (New York, N.Y.)

|September 22, 1995

まとめ

ミトゲン活性化タンパク質キナーゼ (MAPK) は,インターフェロン受容体と相互作用し,早期の遺伝子活性化を調節します. この発見は,MAPKを明らかにしています.

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:

インターフェロン (IFN) は,STATタンパク質のリン酸化によって早期応答遺伝子を活性化します.
IFNシグナリングを制御する正確なメカニズムについては,さらなる解明が必要である.

研究の目的:

インターフェロン-α/β (IFN-α/β) シグナル伝達におけるミトゲン活性化タンパク質キナーゼ (MAPK) の役割を調査する.
MAPKがIFNに対応してJak-STAT経路を調節するかどうかを判断する.

主な方法:

MAPK (ERK2) とIFN-α/β受容体との相互作用に関するインビトロおよびインビボの研究.
MAPKとStat1αのリン酸化と共免疫プレシピテーションを評価するために,IFN-βによる細胞治療.
主要負のMAPK発現を用いたIFN-β誘発転写の分析.

主要な成果:

ミトゲン活性化タンパク質キナーゼ (MAPK),特にERK2は,IFN-α/β受容体と相互作用することが判明しました.
IFN-β治療により誘発されたチロシンリン酸化とMAPKの活性化.
MAPKとStat1αがIFN-β刺激後に共免疫的に precipitated.
支配的な負の構造を持つMAPK信号伝達の抑制は,IFN-β誘発の転写をブロックしました.

結論:

MAPKは,IFN-αおよびIFN-βシグナル伝達経路における規制的な役割を果たしています.
MAPKはJak-STATカスケードを修正し,IFNによる早期応答遺伝子の活性化に影響を与えます.

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