细胞质蛋白GAP被认为是ras基因产物调节的目标
C Calés1, J F Hancock, C J Marshall
1Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Nature
|April 7, 1988
概括
拉斯基因的突变会产生驱动瘤生长的coproteins. 研究人员发现,GAP蛋白与p21ras在效应器部位相互作用,这表明它是效应器部位.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 信号传导传导是指信号的传导.
背景情况:
- 大约30%的人类瘤在ras基因中存在突变,产生p21rascoproteins.
- p21ras 瘤蛋白与瘤的转变表型有关.
- 拉斯蛋白的确切生化功能尚不清楚,尽管它们与GTP/GDP结合,并具有GTPase活性,这表明它们在通过血信号通路调节细胞增殖方面发挥作用.
研究的目的:
- 为了研究ras蛋白的生物化学作用模式.
- 为了确定通过p21ras.调节的生物目标.
- 为了阐明ras蛋白和GAP之间的相互作用.
主要方法:
- 在p21ras和GAP之间进行了相互作用研究.
- 通过GAP对GTPase活性调节的分析.
- 在p21ras.上映GAP的相互作用部位.
主要成果:
- GAP显著增加了正常p21ras的GTPase活性.
- GAP不会影响p21ras蛋白的GTPase活性.
- 在被确定为"效应器"部位的位置上,GAP与p21ras相互作用.
结论:
- 作为p21ras.调节的生物标,GAP受到强烈影响.
- 了解p21ras-GAP相互作用对于理解瘤发育至关重要.
- 这一发现为癌症中RAS介导的信号传导提供了洞察力.
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...
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 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:


