Lysophosphatidic acid LPA1-3 receptors: signaling, regulation and in silico analysis of their putative phosphorylation sites

Lysophosphatidic acid (LPA) is a bioactive lipid with a plethora of roles in the normal function of our organism as well as in the pathogenesis of many diseases. The actions of LPA are mainly mediated through a family of G protein-coupled receptors, which currently is composed of six members; other receptors might participate in LPA actions including a nuclear receptor. In this work, we mainly focus on three of these receptors, i. e.,  LPA 1-3; those that were initially discovered which, have been more extensively studied and that are phylogenetically related among themselves,  as well as with receptors for other bioactive phospholipids, such as those for spingosine 1-phosphate.  The characteristics of these receptors, their patterns of tissue expression, and some of the actions in which they are involved are presented. Regulation of receptor function, including desensitization, internalization and phosphorylation has only been studied for the LPA 1 subtype. However, in silico analysis of potential phosphorylation sites indicate that all of these three receptors are putatively regulated by agonist activation and heterologous stimuli. We think LPA 1-3 receptor regulation constitutes a niche of investigation that is potentially of great importance considering the physiological and pathophysiological actions in which they are involved.