Signaling and biological actions of sphingosine 1-phosphate.
Sphingosine 1-phosphate (S1P) is a product of sphingomyelin (SM) metabolism. It is present in most 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, S1P 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.
Hla
Timothy
T
Department of Physiology, Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030-3501, USA. hla@nso.2uchc.edu
D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D007109:Immunity / Q000502:physiology; D008246:Lysophospholipids / Q000276:immunology / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000276:immunology / Q000502:physiology*
D008246:Lysophospholipids; D011956:Receptors, Cell Surface; C060506:sphingosine 1-phosphate; D013110:Sphingosine