Lysophospholipids (LPs), such as lysophosphatidic acid and sphingosine 1-phosphate, are membrane-derived bioactive lipid mediators. LPs can affect fundamental cellular functions, which include proliferation, differentiation, survival, migration, adhesion, invasion, and morphogenesis. These functions influence many biological processes that include neurogenesis, angiogenesis, wound healing, immunity, and carcinogenesis. In recent years, identification of multiple cognate G protein-coupled receptors has provided a mechanistic framework for understanding how LPs play such diverse roles. Generation of LP receptor-null animals has allowed rigorous examination of receptor-mediated physiological functions in vivo and has identified new functions for LP receptor signaling. Efforts to develop LP receptor subtype-specific agonists/antagonists are in progress and raise expectations for a growing collection of chemical tools and potential therapeutic compounds. The rapidly expanding literature on the LP receptors is herein reviewed.
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 processes including neurogenesis, myelination, angiogenesis, wound healing, and cancer progression. LPA acts through specific G protein-coupled, seven-transmembrane domain receptors. To date, three mammalian cognate receptor genes, lp(A1)/vzg-1/Edg2, lp(A2)/Edg4, and lp(A3)/Edg7, have been identified that encode high-affinity LPA receptors. Here, we review current knowledge on these LPA receptors, including their isolation, function, expression pattern, gene structure, chromosomal location, and possible physiological or pathological roles.
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