PDF(Pubmed)
Abstract：
Secreted phospholipases A2 (sPLA2s) participate in a very broad spectrum of biological processes through their enzymatic activity and as ligands for membrane and soluble receptors. The physiological roles of sPLA2s as enzymes have been very well described, while their functions as ligands are still poorly known. Since the last overview of sPLA2-binding proteins (sPLA2-BPs) 10 years ago, several important discoveries have occurred in this area. New and more sensitive analytical tools have enabled the discovery of additional sPLA2-BPs, which are presented and critically discussed here. The structural diversity of sPLA2-BPs reveals sPLA2s as very promiscuous proteins, and we offer some structural explanations for this nature that makes these proteins evolutionarily highly advantageous. Three areas of physiological engagement of sPLA2-BPs have appeared most clearly: cellular transport and signalling, and regulation of the enzymatic activity of sPLA2s. Due to the multifunctionality of sPLA2s, they appear to be exceptional pharmacological targets. We reveal the potential to exploit interactions of sPLA2s with other proteins in medical terms, for the development of original diagnostic and therapeutic procedures. We conclude this survey by suggesting the priority questions that need to be answered.
摘要：
分泌型磷脂酶A2(sPLA2s)通过它们的酶活性和作为膜和可溶性受体的配体参与非常广泛的生物过程。sPLA2s作为酶的生理作用已经得到了很好的描述，虽然它们作为配体的功能仍然知之甚少。自从10年前sPLA2结合蛋白（sPLA2-BPs）的最后一次概述以来，在这个领域已经发生了几个重要的发现。新的和更灵敏的分析工具使得能够发现额外的SPLA2-BP，在这里介绍和批判性讨论。sPLA2-BPs的结构多样性表明sPLA2是非常混杂的蛋白质，我们为这种性质提供了一些结构解释，使这些蛋白质在进化上具有高度优势。sPLA2-BPs的生理参与的三个领域最清楚地出现：细胞运输和信号传导，和调节sPLA2s的酶活性。由于SPLA2的多功能性，它们似乎是特殊的药理靶点。我们揭示了在医学方面利用sPLA2与其他蛋白质相互作用的潜力，用于开发原始的诊断和治疗程序。我们通过提出需要回答的优先问题来结束这项调查。
