The endothelial differentiation gene-encoded G protein-coupled receptors (Edg Rs) Edg-1, -3, -5, and -8 bind sphingosine 1-phosphate (SIP) and Edg-2, -4, and -7 bind lysophosphatidic acid (LPA), resulting in transduction of cellular signals for proliferation, increased survival, reduced apoptosis, adherence, migration, secretion, and other specific functions. The diversity of signals emanating from each Edg R is in part attributable to coupling to multiple G proteins. One or more Edg Rs are expressed prominently in the cardiovascular, pulmonary, nervous, endocrine, genitourinary, hematological, and immune systems. Expression of Edg Rs is regulated by developmental and postdevelopmental physiological events. The levels of Edg Rs increase in distinctive patterns in many diseases, as exemplified by high levels of Edg-4 in ovarian cancer, whereas none is detected in normal ovarian surface epithelial cells. Although several analogs of LPA and SIP have altered agonist or antagonist activities, potent pharmacological agents have not been identified to date.

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