EPS8とE3B1は,RasからRacへの信号を変換する
G Scita1, J Nordstrom, R Carbone
1Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Nature
|September 28, 1999
まとめ
Eps8とE3b1/Abi-1はRasからRacへの信号を媒介し,Rac特有のグアニンヌクレオチド交換因子 (GEF) 活動を調節する. これらのタンパク質はRasとRacの間で信号を転送する複合体を形成します.
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.
- シグナルトランスデュークション.
背景:
- Racは小さなGTP結合タンパク質で,細胞骨格の変化とc-Junアミノ端末キナーゼ (JNK) 活性を調節する.
- RacはRas媒介の細胞変容に不可欠であり,Ras信号伝達の下流ターゲットの役割を示しています.
- RasやRacのような小さなGTP結合タンパク質間のクロストークを制御する正確な生化学的メカニズムは,完全に理解されていません.
研究 の 目的:
- Ras と Rac. の間の信号伝導を調節する生化学的メカニズムを解明する.
- ラス-ラック信号伝達経路におけるEps8とE3b1/Abi-1の役割を調査する.
- Rac活性化に関与するタンパク質複合体の形成と機能を特徴付ける.
主な方法:
- Eps8,E3b1/Abi-1,およびRac.との相互作用を調査しました.
- グアニンヌクレオチド交換因子 (GEF) の活動を評価するために,in vivoおよびin vitroアッセイを使用しました.
- Eps8,E3b1,Sos-1を含む三複合体の形成を分析した.
主要な成果:
- Eps8とE3b1/Abi-1は,Ras-to-Racの信号伝導に関与することが示されました.
- これらのタンパク質は,Rac特異のグアニンヌクレオチド交換因子 (GEFs) の活動を調節する.
- Eps8,E3b1,Sos-1の安定したトライコンプレックスが特定され,Race固有のGEF活性を in vitroで示した.
結論:
- Eps8は,RasからRacへの信号転送を媒介する上で重要な役割を果たしています.
- Eps8,E3b1,Sos-1を含む複合体の形成は,Racの活動を調節する重要なメカニズムです.
- この研究では,Eps8がRas-Racのシグナリングカスケードにブリッジとして作用するモデルを提案しています.
関連する概念動画
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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Ras is a superfamily...
Cell Polarization by Rho Proteins
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Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...


