Do annexins participate in lipid messenger mediated intracellular signaling? A question revisited
Do annexins participate in lipid messenger mediated intracellular signaling? A question revisited
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DOI：
10.3109/09687688.2012.693210
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发表时间：
2012-11-01
影响因子：
--
通讯作者：
Pikula, Slawomir
中科院分区：
文献类型：
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作者：
Bandorowicz-Pikula, Joanna;Wos, Marcin;Pikula, Slawomir
膜联蛋白是生理上重要的蛋白质，其在钙缓冲中起作用，但也影响膜结构，参与Ca2+依赖性膜修复事件和细胞骨架的重塑。30年前，从肺灌流液、腹膜白细胞、嗜中性粒细胞和肾细胞中分离出的几种肽被证明能抑制磷脂酶A的活性（2）。这些肽被发现来自结构相关的蛋白质：膜联蛋白AnxA1和AnxA2。这些发现提出了一个问题，即膜联蛋白是否参与调节脂质第二信使的产生，从而调节细胞中许多脂质介导的信号通路。最近在膜联蛋白领域的进展也与使用敲除动物模型揭示，这些蛋白质确实是特定的信号通路的重要组成部分。在这篇综述中，我们提供的证据支持这一假设，即膜联蛋白，作为膜结合蛋白和膜横向异质性的组织者，可能通过影响脂质代谢酶（大多数报告指向磷脂酶A（2））和调节这些酶活性的蛋白激酶的分布和活性，参与脂质介导的信号通路。此外，一些实验数据表明，膜联蛋白可以直接与脂质代谢酶相互作用，并在钙依赖或独立的方式，与他们的一些底物和产品。基于这些观察结果，许多研究者认为，膜联蛋白能够连接Ca 2+，氧化还原和脂质信号，以协调重要的细胞对环境刺激的反应。
Annexins are physiologically important proteins that play a role in calcium buffering but also influence membrane structure, participate in Ca2+-dependent membrane repair events and in remodelling of the cytoskeleton. Thirty years ago several peptides isolated from lung perfusates, peritoneal leukocytes, neutrophiles and renal cells were proven inhibitory to the activity of phospholipase A(2). Those peptides were found to derive from structurally related proteins: annexins AnxA1 and AnxA2. These findings raised the question whether annexins may participate in regulation of the production of lipid second messengers and, therefore, modulate numerous lipid mediated signaling pathways in the cell. Recent advances in the field of annexins made also with the use of knock-out animal models revealed that these proteins are indeed important constituents of specific signaling pathways. In this review we provide evidence supporting the hypothesis that annexins, as membrane-binding proteins and organizers of the membrane lateral heterogeneity, may participate in lipid mediated signaling pathways by affecting the distribution and activity of lipid metabolizing enzymes (most of the reports point to phospholipase A(2)) and of protein kinases regulating activity of these enzymes. Moreover, some experimental data suggest that annexins may directly interact with lipid metabolizing enzymes and, in a calcium-dependent or independent manner, with some of their substrates and products. On the basis of these observations, many investigators suggest that annexins are capable of linking Ca2+, redox and lipid signaling to coordinate vital cellular responses to the environmental stimuli.