Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Int J Biol Sci. 2022 Jan 1;18(2):873-888. doi: 10.7150/ijbs.68093. eCollection 2022.
Secreted phospholipases A (sPLAs) 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 sPLAs as enzymes have been very well described, while their functions as ligands are still poorly known. Since the last overview of sPLA-binding proteins (sPLA-BPs) 10 years ago, several important discoveries have occurred in this area. New and more sensitive analytical tools have enabled the discovery of additional sPLA-BPs, which are presented and critically discussed here. The structural diversity of sPLA-BPs reveals sPLAs 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 sPLA-BPs have appeared most clearly: cellular transport and signalling, and regulation of the enzymatic activity of sPLAs. Due to the multifunctionality of sPLAs, they appear to be exceptional pharmacological targets. We reveal the potential to exploit interactions of sPLAs 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.
分泌型磷脂酶 A（sPLA）通过其酶活性和作为膜和可溶性受体配体参与非常广泛的生物学过程。sPLA 作为酶的生理作用已经得到了很好的描述，而它们作为配体的功能仍知之甚少。自 10 年前对 sPLA 结合蛋白（sPLA-BPs）进行全面综述以来，该领域出现了一些重要的发现。新的和更敏感的分析工具使更多的 sPLA-BPs 得以发现，并在此处进行了介绍和批判性讨论。sPLA-BPs 的结构多样性表明 sPLA 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，这使得这些蛋白质在进化上具有很高的优势。sPLA-BPs 在三个生理参与领域的作用最为明显：细胞运输和信号转导，以及 sPLA 酶活性的调节。由于 sPLA 的多功能性，它们似乎是特殊的药理学靶点。我们揭示了在医学方面利用 sPLA 与其他蛋白质相互作用的潜力，以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本综述。
