血清応答要素のc-fosで作用する信号に対する異なるタンパク質標的

R Graham¹, M Gilman

¹Cold Spring Harbor Laboratory, NY 11724.

Science (New York, N.Y.)

|January 11, 1991

まとめ

成長因子は,c-fos 血清応答要素 (SRE) を標的にする細胞信号伝達経路を活性化します. p62TCFを含む2つの異なる経路は,SREに収束し,遺伝子発現を調節する.

科学分野:

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
遺伝子規制遺伝子規制

背景:

c-fos 血清応答要素 (SRE) は,成長因子誘発細胞内信号伝導の重要な核標的である.
信号伝達経路は,タンパク質キナーゼC (PKC) に依存した信号と独立した信号を含むSREに収束します.

研究の目的:

異なるシグナル伝達経路がSREと相互作用する分子メカニズムを解明する.
血清応答因子 (SRF) とp62TCFがSREにおける差異信号応答を媒介する役割を調査する.

主な方法:

変異したSREを用いてSRFを結合するが,p62TCFとの三元複合体の形成を防ぐ.
野生型と変異性SREのPKC活性化剤とPKC独立信号に対する反応を比較した.

主要な成果:

変異したSREは,p62TCFと三元複合体を形成できず,PKC活性化剤に対する反応性を失いました.
この変異したSREは,PKC独立の信号に対する応答を保持し,経路特異の相互作用を示した.
2つの異なるシグナル伝達経路が,SREの離散的な核標的を利用することを実証しました.

結論:

SREは,異なる分子相互作用を通じて,複数の細胞内経路からの信号を統合します.
p62TCFのような経路固有の補助因子は,シグナリングの特異性に寄与する.
これらの発見は,一般的なDNA要素が多様な生物学的反応を媒介する方法を理解するための分子基盤を提供します.

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