スプラウティは,Ras信号伝達の細胞内阻害剤である
Cell
|March 25, 1999
まとめ
スプラウティは,Ras経路を阻害する細胞内タンパク質です. この発見は,細胞のシグナル伝達と発達の調節におけるその役割を明らかにし,様々な受容体チロシンキナーゼに影響を与えます.
科学分野:
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学とは
- 細胞シグナル伝達 細胞信号伝達
背景:
- スプラウティは当初,ドロソフィラの表皮成長因子受容体 (EGFR) 信号伝達の阻害剤として特定されました.
- 芽の突然変異は,ドロソフィラの眼に過剰な細胞の採用を引き起こし,発達過程におけるその役割を示している.
研究 の 目的:
- EGFRシグナル伝達を超えて,Sproutyの細胞の局所化とより広範な機能的役割を調査する.
- Sproutyが信号伝達経路に抑制効果を発揮する分子メカニズムを解明する.
主な方法:
- 他の受容体チロシンキナーゼ (Torso,Sevenless) とフィブロブラスト成長因子受容体 (FGFR) 信号伝達との遺伝的相互作用の研究.
- Sproutyのサブセルラー局所を決定するための生化学分析.
- Ras経路内の結合パートナーを特定するためのタンパク質-タンパク質相互作用測定法.
主要な成果:
- スプラウティは,プラズマ膜に関連した細胞内タンパク質であり,以前の細胞外局所化仮説と矛盾しています.
- スプラウティは,多種受容体チロシンキナーゼ (Torso,Sevenless,FGFRなど) と遺伝的に相互作用する.
- スプラウティは,細胞内Ras経路のコンポーネント,DrkとGap1.1に直接結合する.
結論:
- スプラウティは,Ras経路信号伝導の広範な細胞内阻害体として機能します.
- プラズマ膜での局所化とRas経路の成分との相互作用は,開発における広範な抑制作用のメカニズムを提供します.
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.
Ras is a superfamily...
Ras is a superfamily...
Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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 JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
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...


