MINIREVIEW Lysophosphatidic Acid Receptors

Lysophosphatidic acid (LPA) is a simple bioactive phospholipid with diverse physiological actions on many cell types. LPA induces proliferative and/or morphological effects and has been proposed to be involved in biologically important pro-cesses including neurogenesis, myelination, angiogenesis, wound healing, and cancer progression. LPA acts through spe-cific G protein-coupled, seven-transmembrane domain recep-tors. To date, three mammalian cognate receptor genes, lpA1/ vzg-1/Edg2, lpA2/Edg4, and lpA3/Edg7, have been identified that encode high-affinity LPA receptors. Here, we review cur-rent knowledge on these LPA receptors, including their isola-tion, function, expression pattern, gene structure, chromo-somal location, and possible physiological or pathological roles. Lysophosphatidic acid (LPA; 1-acyl-2-sn-glycerol-3-phos-phate) is a naturally occurring lysophospholipid (LP) that activates diverse cellular actions on many cell types (Fig. 1). It is also an intermediate in de novo biosynthesis of mem-brane phospholipids. Although all cells contain small amounts of LPA associated with membrane biosynthesis, some cellular sources can produce significant amounts of extracellular LPA such as activated platelets, which account for the LPA found in serum (Eichholtz et al., 1993). Sphin-gosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) also activate cellular responses in many cell types (Spiegel et al., 1998). LPA, S1P, and SPC each activate spe-cific members of the G protein-coupled receptor (GPCR) su-perfamily. Lysophospholipid GPCRs are encoded by the lp genes (also referred to by various orphan receptor names such as vzg/ edg/mrec/gpcr26/h218/agr16/nrg-1), of which there are currently eight known members (Fig. 2). Three of these genes (lpA1–3) encode high-affinity LPA receptors (Hecht et al.