SWAP-70是一种关氨酸核酸交换因子,它介导了膜的信号传递
Masahiro Shinohara1, Yoh Terada, Akihiro Iwamatsu
1Department of Applied Biological Chemistry, Faculty of Agricultural and Life Science, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
Nature
|April 19, 2002
概括
SWAP-70被确定为一种新型的Rac-guanine核酸交换因子 (GEF),可以结合酸-3,4,5-三酸盐 (PtdIns(3,4,5) P3). 这种蛋白质调解生长因子诱导的细胞膜和Rac激活,独立于Ras信号传递.
科学领域:
- 细胞信号传递和分子生物学
- 脂质的第二信使途径.
- 细胞骨动力学 细胞骨动力学
背景情况:
- 酸-3-OH激酶 (PI(3) K) 产生酸-3,4,5-三酸盐 (PtdIns(3,4,5) P3),这是一个关键的脂质第二信使.
- PtdIns{3,4,5) P3调节关键细胞过程,包括激活,存活和细胞骨重组.
- 全套PtdIns的目标和它们的功能仍然不完全理解.
研究的目的:
- 为了确定脂氨醇-3,4,5-三酸盐 (PtdIns(3,4,5) P3) 的新标.
- 研究SWAP-70在信号传导途径中的作用.
- 阐明SWAP-70调节细胞膜动态和Rac激活的机制.
主要方法:
- 证明了SWAP-70对PtdIns的特定结合{3,4,5) P3.3.
- 使用生长因子刺激 (EGF,PDGF) 来观察SWAP-70局部化和膜.
- 雇佣的突变SWAP-70缺乏PtdIns(3,4,5) P3结合能力来评估功能需求.
- 评估了SWAP-70在Rac.上进行的关氨酸核酸交换活动.
- 研究了SWAP-70缺乏纤维细胞,以证实其在Rac激活和膜变中的作用.
主要成果:
- SWAP-70 特别结合了酸丁酸-3,4,5-三酸盐 (PtdIns(3,4,5) P3).
- 增长因子刺激诱导SWAP-70以PI(3) K依赖的方式转移到细胞膜.
- 突变的SWAP-70无法结合PtdIns{3,4,5) P3被废除的生长因子诱导的膜.
- SWAP-70作为一个Rac-guanine核酸交换因子 (GEF),催化PtdIns(3,4,5) 在Rac.上P3-依赖的核酸交换.
- 缺少SWAP-70的纤维细胞在EGF刺激时表现出受损的膜和降低的Rac激活.
结论:
- SWAP-70是一种新型的Rac-GEF,它直接将PtdIns{3,4,5) P3与Rac激活联系起来.
- SWAP-70通过中介从氨酸激酶受体传递给 Rac 的信号,控制了独立于 Ras. Ras. 的膜乱.
- 这项研究揭示了一个新的信号轴,涉及SWAP-70调节细胞形态和对生长因子的反应.
相关概念视频
Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
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...
SNAREs and Membrane Fusion
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
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.
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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:


