活性化されたPDGF受容体へのGAPの結合
A Kazlauskas1, C Ellis, T Pawson
1Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Science (New York, N.Y.)
|March 30, 1990
まとめ
血小板由来成長因子 (PDGF) 信号伝達は,Ras GTPase活性化タンパク質 (GAP) を含む. PDGFがその受容体に結合すると,GAPを誘導し,最大限の結合のために受容体キナーゼ活性と特定のチロシンリン酸化部位を必要とします.
科学分野:
- 細胞の信号伝達経路は,
- 分子生物学は分子生物学である.
- 腫瘍遺伝子の研究
背景:
- ラス原発がん遺伝子製品は,細胞内信号伝達器の鍵である.
- Ras GTPaseアクティベータータンパク質 (GAP) は,Rasからの信号を媒介する.
- 血小板由来成長因子 (PDGF) 受容体は,リガンド結合時にシグナリングカスケードを開始します.
研究 の 目的:
- PDGF受容体とGAPの相互作用を調査する.
- PDGF受容体とのGAP結合の分子要件を解明する.
主な方法:
- 人間のPDGF受容体を発現するように設計された犬の上皮細胞を使用した.
- GAP複合体の形成に対するPDGF結合の効果を研究した.
- 変異したPDGF受容体を採用し,受容体-GAP関連性の重要な領域と活動を特定しました.
主要な成果:
- PDGF結合は,GAPとPDGF受容体間の複合体の形成を誘導し,全GAP分子の約10%で発生した.
- 受容体とGAPの最大関連は,活性受容体キナーゼ機能を必要とする.
- オートフォスフォリレーション部位における特定の酸化可能なチロシン残留物は,堅固なGAP複合化に不可欠でした.
結論:
- PDGF受容体とGAPの相互作用は,PDGF媒介の細胞内信号伝達の重要なステップである.
- 受容体キナーゼ活性と特定のチロシンリン酸化部位は,GAPの効率的な募集に不可欠です.
- この相互作用は,成長因子受容体によるRas信号伝達経路の複雑な調節を強調しています.
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