多个Ras功能可以促进哺乳动物细胞转化
M A White1, C Nicolette, A Minden
1Cold Spring Harbor Laboratory, New York 11724.
Cell
|February 24, 1995
概括
研究人员在Ha-Ras效应环中发现了特定的突变. 这些突变有助于分离与下游效应者的相互作用,揭示了诸如Raf1在细胞转化中的多个组成部分.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 哈拉斯是细胞信号通路的关键调节者.
- 哈拉斯的失调与各种癌症有关.
- 了解Ha-Ras效应因子相互作用对于向治疗至关重要.
研究的目的:
- 开发一种方法来隔离Ha-Ras效应环突变.
- 研究特定突变如何影响Ha-Ras与下游效应器的相互作用.
- 阐明不同效应因子在Ha-Ras介导的细胞转化中的作用.
主要方法:
- 使用了两种混合相互作用的通用方法.
- 生成并分析了哈拉斯效应环突变体.
- 评估了细胞转化,焦点形成和下游效应器激活.
主要成果:
- 孤立突变可以选择性地改变Ha-Ras与效应器的相互作用.
- 这些突变减弱了Ha-ras ((G12V) 转化,但保留了互补活性.
- 证明了不同下游组件的协同转换诱导和激活.
- 展示了 raf1 突变体对转化缺陷的救援,恢复了相互作用.
结论:
- 多个细胞组件,包括Raf1,被Ha-Ras.激活.
- 这些成分共同促进Ha-Ras诱导的哺乳动物细胞转化.
- 开发的方法允许剖析复杂的信号网络.
相关概念视频
Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
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...
Cell 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,...
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:
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...


