Secreted Phospholipases A2 - not just Enzymes: Revisited.

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.