Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid.

A cDNA homologous to that encoding sheep Edg2 protein was cloned from a human lung cDNA library. The full-length sequence encodes a 364-amino acid protein which belongs to the superfamily of guanine nucleotide-binding (G) protein-coupled receptors. Human Edg2 mRNA is widely distributed in human tissues with the highest abundance in brain. HEK293 cells expressing the human Edg2 protein showed an elevated response to lysophosphatidic acid (LPA) in a serum response element reporter gene assay, which was LPA concentration-dependent and specific to LPA compared to other lysophospholipids. Over-expression of human Edg2 in CHO cells correlated with increases in specific binding of [3H]-LPA. Recently, the mouse counterpart of Edg2 protein also was identified as a receptor for LPA (Hecht et al., 1996, J. Cell Biol. 135, 1071). Therefore, it is concluded that the human Edg2 protein functions as a cellular receptor for LPA.