Signaling and biological actions of sphingosine 1-phosphate

Sphingosine 1-phosphate (S1P) is a product of sphingomyelin (SM) metabolism. It is present inmost eukaryotic organisms; however, in higher vertebrates (bony fishes to mammals), it is utilized as a regulator of cell function by binding to extracellular receptors. Its role as a second messenger function was originally proposed; however, the unequivocal role of S1P as a second messenger in higher eukaryotes is lacking at present. As an extracellular mediator, S1P binds to a family of G-protein-coupled receptors named S1P(1-5), originally referred to as (EDG-1, 3, 5, 6 and 8). These receptors couple to multiple G-proteins and regulate intracellular signaling pathways. Most tissues express one or more S1P receptor subtypes; therefore, SIP is known as a multifunctional physiologic mediator. Its precise physiologic roles in multiple organ systems are just beginning to be elucidated; however, at present, regulation of cardiogenesis, vascular system formation, oocyte survival and immune cell trafficking has been recently reported. Currently, a S1P receptor agonist, is undergoing clinical trials as an agent to fight organ transplant rejection. Since S1P is a fundamental multifunctional mediator, better understanding of the biology of S1P holds great promise to develop novel tools to control various diseases. (C) 2003 Published by Elsevier Science Ltd.