在Raf-1被14-3-3蛋白激活时,Raf-1被14-3-3蛋白激活
W J Fantl1, A J Muslin, A Kikuchi
1Daiichi Research Center, Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco 94143.
Nature
|October 13, 1994
概括
研究人员发现14-3-3蛋白与Raf-1结合,增强其激酶活性. 这种相互作用对细胞生长和分化过程至关重要,为Raf-1调节提供了新的见解.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- Raf-1 是一种关键的蛋白质,它调解细胞生长和分化.
- 目前尚不完全了解Raf-1的氨酸/氨酸激酶活性的调节.
- 拉夫-1与p21ras结合在一起.
研究的目的:
- 为了确定与Raf-1相互作用的蛋白质.
- 了解调节Raf-1激酶活动的过程.
主要方法:
- 酵母的双混合系统用于识别相互作用的蛋白质.
- 在Xenopus卵细胞中的表达以研究蛋白质功能.
主要成果:
- 确定了14-3-3 zeta和14-3-3 beta作为Raf-1相互作用蛋白.
- 14-3-3蛋白增强了Raf-1在Xenopus卵细胞中的活性.
- 14-3-3蛋白质促进了Raf-1-依赖性卵细胞的成熟.
结论:
- 14-3-3蛋白质是Raf-1激酶活性的新型调节者.
- 14-3-3蛋白和Raf-1之间的相互作用对细胞信号通路很重要.
- 这一发现为控制Raf-1功能提供了一个新的机制.
相关概念视频
01:14Rab 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...
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...
01:25Rab 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...
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...