Structural and functional characteristics of S1P receptors

The sphingosine-1-phosphate (SIP) family of G protein-coupled receptors (GPCR) regulates essential cellular processes Such as proliferation, migration, cytoskeletal organization, adherens junction assembly, and morphogenesis. SIP, a product from the breakdown of sphingomyelin, binds to the five members of this receptor family, S1P(1), S1P(2), S1P(3), S1P(4), and S1P(5), previously referred to as endothelial differentiation gene (EDG)-1, -5, -3, -6, and -8. SIP receptors are widely expressed in different tissues, so it is not surprising that the SI P receptor family regulates many physiological processes, such as vascular maturation, cardiac development, lymphocyte trafficking, and vascular permeability. FTY720, a new S1P receptor agonist, is undergoing clinical trials as an immunosuppressor. Understanding the physiological role of these receptors and the basics of the ligand-receptor interaction will potentially provide new therapies to control a variety of diseases. (C) 2004 Wiley-Liss, Inc.