Regulation of Mammalian Physiology, Development, and Disease by the Sphingosine 1-Phosphate and Lysophosphatidic Acid Receptors

The synthesis of LPA and S1P occurs both intracellularly and extracellularly. S1P and LPA can be found in high nanomolar to low micromolar concentrations in the blood and lymph and low concentrations in normal tissue. Degradation of either LPA or S1P can occur in either a reversible or irreversible fashion. Dephosphorylation is mediated by a number of lipid phosphate phosphohydrolases (LPP), all of which are integral membrane proteins, but one of which, LPP1, localizes with its active site facing the extracellular space. Autotaxin's property as a transporter is ancillary to its enzymatic activity in the biosynthesis of LPA. In vitro binding assays showed ATX binding to lymphocytes or activated platelets in an integrin-dependent fashion, and in both instances, ATX was found in association with these cells in vivo, in high endothelial venules or thrombi, respectively.