The caveolar paradox: suppressing, inducing, and terminating eNOS signaling.
The caveolar paradox: suppressing, inducing, and terminating eNOS signaling.
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小凹悖论：抑制、诱导和终止 eNOS 信号传导。
DOI：
10.1161/01.res.88.2.129
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发表时间：
2001
影响因子：
20.1
通讯作者：
R. Kelly
中科院分区：
文献类型：
--
作者：
O. Féron;R. Kelly
现在已经确定，专门的质膜脂质微环境（Simons和Toomre称为脂筏）1参与各种信号转导过程。脂筏的一个子集（主要含有胆固醇和鞘脂）存在于质膜小泡中，称为小窝。术语小窝（“小洞穴”）是在40多年前引入的，用于描述通过电子显微镜在多种细胞类型中鉴定的质膜内陷。最初，这些50- 100-nm的质膜小泡被证明参与大分子的跨细胞运输（转胞吞作用）和小分子的摄取（potocytosis）。2然而，直到最近，随着小凹蛋白作为小凹的结构外壳组分的鉴定，已经认识到小窝通过确保信号分子的区室化而参与信号转导，如G蛋白和酪氨酸激酶相关受体，以及内皮型一氧化氮合酶（eNOS）。这种不同的角色的识别提出了一个问题，即同一个细胞器如何能够同时参与这些明显不同的功能。然而，在eNOS的情况下，最近的数据表明，这两种功能（即，作为信号平台和细胞内运输模块），事实上，密切相关和互补。
虽然eNOS和小窝蛋白都有几个被认为参与蛋白质-蛋白质相互作用的共有序列，但eNOS和小窝蛋白之间功能关联的证据仅存在于小窝蛋白支架结构域（CSD）中，这是一个位于小窝蛋白C-末端部分的20个氨基酸的质膜区域。小窝蛋白的支架结构域促进了预组装寡聚蛋白的产生，此外，还使这些不同的信号蛋白保持在它们的关闭状态。然而，注意，CSD共识结合序列的存在并不一定意味着给定的蛋白质...
It is now established that specialized plasmalemmal lipid microenvironments, termed lipid rafts by Simons and Toomre,1 take part in various signal transduction processes. One subset of lipid rafts (which contain mostly cholesterol and sphingolipids) is found in plasmalemmal vesicles termed caveolae. The term caveolae (“little caves”) was introduced more than 40 years ago to describe plasma membrane invaginations identified by electron microscopy in a wide variety of cell types. Originally, these 50- to 100-nm plasmalemmal vesicles were shown to participate in the transcellular transport of macromolecules (transcytosis) and in the uptake of small molecules (potocytosis).2 However, it is only recently, with the identification of caveolins as the structural coat component of caveolae, that it has been recognized that caveolae are involved in signal transduction by ensuring the compartmentation of signaling molecules, such as G protein and tyrosine kinase–associated receptors, as well as endothelial nitric oxide synthase (eNOS). The identification of such distinct roles raises the question of how the same organelle can participate in these apparently quite different functions simultaneously. However, in the case of eNOS, recent data suggest that both of these functions (ie, as signaling platforms and intracellular trafficking modules) are, in fact, intimately related and complementary.
Although both eNOS and caveolins have several consensus sequences that have been proposed to participate in protein-protein interactions, evidence for a functional association between eNOS and caveolins exists only for the caveolin scaffolding domain (CSD), a juxtamembrane region of 20 amino acids in the C-terminal moiety of caveolin.4 Like other modular protein domains, the scaffolding domain of caveolin facilitates the generation of preassembled oligomeric proteins and, in addition, maintains these various signaling proteins in their off state.2 3 4 Note, however, that the presence of a CSD consensus–binding sequence does not necessarily imply that a given protein …
影响因子：
29.4
作者：
Shah, V;Toruner, M;Groszmann, RJ
通讯作者：
Groszmann, RJ