Lysophosphatidic acid (LPA; 1- or 2-acyl-sn-glycero-3-phosphate) is a bioactive phospholipid with mitogenic and/or morphological effects on many cell types. In addition, LPA has been reported to play important roles in various biological processes. It was originally thought that the cellular effects of LPA are mediated by three subtypes of G-protein-coupled receptors: LPA(1)/Edg2, LPA(2)/Edg4, and LPA(3)/Edg7. They share 50-57% amino acid identities and, together with five sphingosine-1-phosphate receptors (S1P(1)/Edg1, S1P(2)/Edg5, S1P(3)/Edg3, S1P(4)/Edg6, and S1P(5)/Edg8), comprise the endothelial cell differentiation gene (Edg) family. However, even after finding of the Edg family LPA receptors, the existence of an additional LPA receptor(s) has been implied by several reports. In 2003, we identified p2y9/GPR23 as a fourth LPA receptor, LPA(4), which is structurally distant from the Edg family LPA receptors. LPA(4)/p2y9/GPR23 has stimulated identification of two additional LPA receptors, LPA(5)/GPR92/GPR93 and LPA(6)/p2y5. These findings made us aware of the existence of a novel "non-Edg" LPA receptor family. This review article focuses on the identification, properties and possible functions of the non-Edg family LPA receptors: LPA(4)/p2y9/GPR23, LPA(5)/GPR92/GPR93 and LPA(6)/p2y5.
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