成長因子受容体上の明確なフォスフォチロシンは,異なるシグナル伝達経路を媒介する特定の分子と結合します
W J Fantl1, J A Escobedo, G A Martin
1Howard Hughes Medical Institute, University of California, San Francisco 94143.
Cell
|May 1, 1992
まとめ
血小板由来成長因子 (PDGF) 受容体は,GTPase活性化タンパク質 (GAP) とフォスファディチルイノシトール3-キナーゼ (PI3-キナーゼ) を異なる部位で結合する. これらの相互作用は,PDGFが刺激するDNA合成に極めて重要です.
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
背景:
- 血小板由来成長因子 (PDGF) 受容体は,細胞の成長と増殖の主要な調節体である.
- それは,SH2ドメインを含むGTPase活性化タンパク質 (GAP) とフォスファディチルイノシトール3-キナーゼ (PI3-キナーゼ) などの細胞内シグナル伝達タンパク質と相互作用します.
研究 の 目的:
- PI3-キナーゼとGAPに対するPDGF受容体の特定の結合部位を特定する.
- PDGF媒介シグナル伝達におけるこれらの相互作用の機能的意義を解明する.
主な方法:
- PI3-キナーゼとGAP結合を競争的に阻害するためにPDGF受容体配列を代表するフォスフォチロシンを含むペプチドを使用した.
- PDGF受容体の特定された結合部位に点変異を導入した.
主要な成果:
- PI3-キナーゼは,PDGF受容体の特定の配列モチーフ内の2つの異なるフォスフォチロジン残基に結合します.
- これらのPI3-キナーゼ結合部位における突然変異はPI3-キナーゼ関連を廃止し,PDGF刺激によるDNA合成を阻害した.
- GAP結合部位の変異は,GAP結合とリン酸化を阻害したが,PI3-キナーゼ結合には影響せず,DNA合成にも大きな影響を与えた.
結論:
- GAPとPI3-キナーゼは,PDGF受容体の分離されたフォスフォチロシンを含む配列モチーフに結合する.
- PI3-キナーゼ結合部位は,PDGF刺激によるDNA合成を媒介する上で重要であり,GAP結合部位は,より小さな役割を果たしている.
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