EPS8和E3B1将信号从Ras转换为Rac的信号
G Scita1, J Nordstrom, R Carbone
1Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Nature
|September 28, 1999
概括
Eps8和E3b1/Abi-1通过调节Rac特定的关氨酸核酸交换因子 (GEF) 活动来调节Ras到Rac的信号. 这些蛋白质形成一个复合体,在Ras和Rac之间传输信号.
科学领域:
- 细胞信号传递途径 细胞信号传递途径
- 分子生物学分子生物学
- 信号传导传导是指信号的传导.
背景情况:
- Rac是一种小的GTP结合蛋白,调节细胞骨变化和c-Jun氨基终端激酶 (JNK) 活性.
- Rac对于Ras介导的细胞转化至关重要,这表明它作为Ras信号传递的下游目标的作用.
- 控制像Ras和Rac这样的小GTP结合蛋白之间的交叉交谈的精确生物化学机制尚未完全理解.
研究的目的:
- 阐明调节Ras和Rac之间的信号传导的生化机制.
- 研究Eps8和E3b1/Abi-1在Ras-Rac信号通路中的作用.
- 描述参与Rac激活的蛋白质复合体的形成和功能.
主要方法:
- 研究了Eps8,E3b1/Abi-1和Rac.之间的相互作用.
- 使用体内和体内测试来评估瓜核酸交换因子 (GEF) 活动.
- 分析了涉及Eps8,E3b1和Sos-1的三复合体的形成.
主要成果:
- 已经证明Eps8和E3b1/Abi-1参与了Ras-to-Rac信号传输.
- 这些蛋白调节了Rac特异的氨酸核酸交换因子 (GEFs) 的活性.
- 确定了Eps8,E3b1和Sos-1的稳定三复合体,在体外显示了Rac特定的GEF活性.
结论:
- Eps8在调解从Ras到Rac的信号传输方面发挥着至关重要的作用.
- 形成一个涉及Eps8,E3b1和Sos-1的复合体是调节Rac活动的关键机制.
- 这项研究提出了一个模型,其中Eps8在Ras-Rac信号级联中充当桥梁.
相关概念视频
02:38The 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...
01:21Cell Polarization by Rho Proteins
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
01:25Rab 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.
01:24Small 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:
01:07MAPK 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...
02:38The 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...