对Ras in Raf激活的要求通过将Raf准到等离子体膜来克服
S J Leevers1, H F Paterson, C J Marshall
1Section of Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, UK.
Nature
|June 2, 1994
概括
拉斯作为Raf的膜,一个关键的蛋白质激酶在细胞信号传递. 这种定位对于Raf激活至关重要,其他信号也对这个过程有所贡献.
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
- 生物化学 生物化学
背景情况:
- 一个保存的信号通路涉及Ras,Raf,MAP-激酶激酶和MAP激酶.
- 拉斯-GTP与Raf相互作用,但没有观察到Ras-GTP在体外直接激酶激活.
- 激活的Raf不需要Ras,这表明Ras有不同的作用.
研究的目的:
- 调查Ras在Raf激活中的作用.
- 为了确定Ras是否需要将Raf定位到等离子体膜以激活.
- 阐明Ras影响Raf活动的机制.
主要方法:
- 同免疫沉试验检测Ras和Raf相互作用.
- 试管体内激酶测试以评估Raf活性.
- 融合蛋白质结构:将K-Ras(4B) 膜局部化信号连接到Raf.
- 在表达工程 Raf 结构的细胞中分析 Raf 激活.
主要成果:
- Ras-GTP在体外没有直接刺激Raf激酶活性.
- 在活性,溶解的Raf的制剂中没有检测到Ras.
- 在表达活性Ras的细胞中,Raf与等离子体膜结合.
- 具有K-Ras(4B) 膜局部化信号的Raf构造是构成性活跃的,并由EGF进一步激活,独立于Ras.
结论:
- 拉斯 (Ras) 作为Raf (Raf) 的一个受调节的,与膜结合的.
- 由Ras介导的等离子膜定位对于Raf激活至关重要.
- 除了Ras之外,还有其他信号事件有助于Raf激活.
更多相关视频
07:49Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
06:44Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
Published on: March 1, 2024
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...
Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
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...
