通过Akt (蛋白激酶B) 对Raf的酸化和调节
1Institute of Medical Virology, University of Zurich, Gloriastrasse 30/32, CH-8028 Zurich, Switzerland.
Science (New York, N.Y.)
|November 27, 1999
概括
蛋白质激酶Akt直接化Raf,抑制Raf-MEK-ERK通路. 这种相互作用将癌细胞的反应从增长停止转变为增殖,揭示了信号通路之间的交叉对话.
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
- 癌症研究 癌症研究
背景情况:
- 蛋白激酶Raf调节关键细胞过程,包括增殖,生长停止,亡和分化.
- 蛋白激酶B (Akt) 是细胞反应的关键调节者,在与Raf不同的信号通路中运行.
- 信号通路之间的交叉交谈可以显著影响细胞行为和疾病状态.
研究的目的:
- 研究Akt和Raf信号通路之间的相互作用.
- 阐明Akt影响Raf活动和细胞反应的分子机制.
- 确定这种相互作用对癌细胞增殖和细胞周期调节的影响.
主要方法:
- 在Raf的活体酸化分析由Akt.
- 评估Raf-MEK-ERK信号通路的激活情况.
- 在人类乳腺癌细胞系中评估细胞反应,包括增殖和细胞循环停止.
主要成果:
- 阿克特直接与其调节域中的保存的血清残留物Raf相互作用并酸化Raf.
- 通过Raf的Akt介导酸化抑制了Raf-MEK-ERK信号级联的激活.
- 这种信号交叉对话促进了增殖,并将细胞表型从细胞循环停止转移到乳腺癌细胞的增殖.
结论:
- Akt和Raf信号通路在Raf蛋白水平上表现出直接的分子交叉交谈.
- 阿克特对Raf的酸化作为一个关键开关,调节癌症中的细胞反应.
- 了解这种相互作用为在癌症治疗中准联合信号通路提供了分子基础.
相关概念视频
02:54Protein Kinases and Phosphatases
15.0K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.0K
02:54Protein Kinases and Phosphatases
4.4K
No description available
4.4K
01:02Phosphorylation
53.7K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
53.7K
02:58Regulated Protein Degradation
8.8K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K
02:58Regulated Protein Degradation
3.1K
No description available
3.1K
02:04Covalently Linked Protein Regulators
8.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.8K