Ras和Rap1A中的异质氨基酸指定了对GAP蛋白的敏感性
K Zhang1, A G Papageorge, P Martin
1Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892.
概括
Ras和Rap1A蛋白中的不同氨基酸控制它们对GTPase激活蛋白 (GAPs) 的敏感性. 这种敏感性是独立于Ras Ras的.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 生物化学 生物化学
- 遗传学 是一个遗传学.
背景情况:
- 拉斯蛋白是细胞信号通路的关键调节者.
- GTP酶激活蛋白 (GAPs) 通过促进GTP水解来调节Ras活性.
- NF1-GRD和Rap-GAP是不同的类别的GAP,具有不同的基质特异性.
研究的目的:
- 调查Ras和Rap1A对不同GAPs敏感性的分子决定因素.
- 阐明GAP灵敏度与Ras.的转化潜力之间的关系.
主要方法:
- 拉斯拉普化学蛋白质的构造和分析.
- 测试GTPase活动和细胞转化.
- 位点定向突变发生,以确定关键氨基酸残留物.
主要成果:
- 在Ras和Rap1A中,不同的氨基酸区域对Ras-GAP,NF1-GRD和Rap-GAP具有不同的敏感性.
- 氨基酸对效应器区域的炭基末端介导Ras-GAP和细胞质Rap-GAP敏感性.
- 特定的Ras残留物 (61-65) 赋予Ras-GAP灵敏度,而对于Rap-GAP灵敏度需要更大的Rap1A段.
结论:
- 拉斯和Rap1A具有不同的氨基酸序列,这决定了它们与特定GAP的相互作用.
- 拉斯的转化潜力及其对拉斯-GAP的敏感性至少部分独立.
- 了解这些分子相互作用对于破译复杂的细胞信号网络至关重要.
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...
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:
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...


