人类Sos1:一个关氨酸核酸交换因子Ras,它与GRB2结合
P Chardin1, J H Camonis, N W Gale
1Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, Valbonne, France.
概括
研究人员确定了hSos1,这是一种对Ras信号传递至关重要的人类蛋白质. 它作为一种关氨酸核酸交换因子,与GRB2相互作用,将受体氨酸激酶与Ras通路连接起来.
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
- 遗传学 是一个遗传学.
背景情况:
- 德洛索菲拉 (Drosophila) 中的七无之子 (Sos) 基因调节Ras信号传递.
- CDC25是一种酵母瓜氨酸核酸交换因子,用于 Ras.
- 受体氨酸激酶 (RTKs) 激活Ras信号通路.
研究的目的:
- 为了识别和描述Drosophila Sos.的人类同类.
- 为了确定人类Sos同类 (hSos1) 在Ras信号传输中的功能.
- 阐明hSos1,GRB2和RTK之间的相互作用.
主要方法:
- 补充DNA (cDNA) 的隔离和测序.
- 在酵母中进行功能补充测试.
- 在体外瓜核酸交换试验.
- 在体内和体外蛋白质相互作用研究 (共免疫沉).
主要成果:
- 孤立的人类cDNA编码hSos1,一种广泛表达的蛋白质.
- 证明了hSos1的CDC25相关的域补充了酵母CDC25的功能.
- 显示的hSos1刺激了哺乳动物Ras蛋白的关氨酸核酸交换.
- 已证实hSos1通过其碳素终端域和GRB2的SH3域与GRB2相互作用.
- 在过度表达hSos1.1的哺乳动物细胞中观察到瓜核酸交换活性增加.
结论:
- hSos1作为Ras蛋白的关氨酸核酸交换因子.
- GRB2-hSos1复合体介导RTK与Ras信号通路的合.
相关概念视频
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
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...
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:
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
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...


