サイトプラズマタンパク質のGAPは,ras遺伝子産物による調節のための標的として関与しています
C Calés1, J F Hancock, C J Marshall
1Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Nature
|April 7, 1988
まとめ
ras遺伝子の変異により,腫瘍の成長を促すオンコプロテインが生成されます. 研究者らは,GAPタンパク質が効果因子部位でp21rasと相互作用することを発見し,それが効果因子部位であることを示唆した.
科学分野:
- 分子生物学は分子生物学である.
- 腫瘍学 腫瘍学
- シグナルトランスデュークション.
背景:
- 人間の腫瘍の約30%は,ras遺伝子の変異を宿し,p21rasオンコプロテインを生成します.
- p21rasオンコプロテインは,腫瘍の変形フェノタイプに関与しています.
- rasタンパク質の正確な生化学的機能は不明であるが,GTP/GDPと結合し,GTPアゼ活性を有し,プラズマ膜シグナル伝達経路を通じて細胞増殖を調節する役割を果たすことを示唆している.
研究 の 目的:
- rasタンパク質の生化学的作用を調査する.
- p21ras.による調節のための生物学的標的を特定する.
- rasタンパク質とGAPの相互作用を解明する.
主な方法:
- p21rasとGAPの相互作用に関する研究.
- GAPによるGTPアゼ活性調節の分析.
- p21ras.上のGAPの相互作用部位をマッピングする.
主要な成果:
- GAPは,正常なp21rasのGTPアゼ活性を劇的に増加させる.
- GAPは,p21rasオンコプロテインのGTPase活性に影響を与えない.
- GAPは,p21rasと"効果因子"部位として特定された部位で相互作用する.
結論:
- GAPは,p21ras.によって調節される生物学的標的として強く関与しています.
- p21ras-GAPの相互作用を理解することは,腫瘍の発達を理解するために重要です.
- この発見は,がんにおけるRAS媒介信号伝導に関する洞察を提供します.
関連する概念動画
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:


