title: Point-counterpoint of sphingosine 1-phosphate metabolism.
abstract: Sphingosine 1-phosphate (S1P), an evolutionarily conserved bioactive lipid mediator, is now recognized as a potent modulator of cell regulation. In vertebrates, S1P interacts with cell surface G protein-coupled receptors of the EDG family and induces profound effects in a variety of organ systems. Indeed, an S1P receptor agonist is undergoing clinical trials to combat immune-mediated transplant rejection. Recent information on S1P receptor biology suggests potential utility in the control of cardiovascular processes, including angiogenesis, vascular permeability, arteriogenesis, and vasospasm. However, studies from diverse invertebrates, such as yeast, Dictyostelium, Drosophila, and Caenorhabditis elegans have shown that S1P is involved in important regulatory functions in the apparent absence of EDG S1P receptor homologues. Metabolic pathways of S1P synthesis, degradation, and release have recently been described at the molecular level. Genetic and biochemical studies of these enzymes have illuminated the importance of S1P signaling systems both inside and outside of cells. The revelation of receptor-dependent pathways, as well as novel metabolic/intracellular pathways has provided new biological insights and may ultimately pave the way for the development of novel therapeutic approaches for cardiovascular diseases.
authors.affiliation: Children's Hospital of Oakland Research Institute, Oakland, Calif, USA.
authors.forename: Julie D
authors.initials: JD
authors.lastname: Saba
authors.forename: Timothy
authors.initials: T
authors.lastname: Hla
mesh_terms: D000446:Aldehyde-Lyases / Q000378:metabolism; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005658:Fungi / Q000378:metabolism; D006801:Humans; D007448:Invertebrates / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D010944:Plants / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D049312:Receptors, Lysophospholipid; D015290:Second Messenger Systems / Q000502:physiology; D013045:Species Specificity; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism*; D014714:Vertebrates / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D000446:Aldehyde-Lyases; D008246:Lysophospholipids; D008565:Membrane Proteins; D010744:Phosphoric Monoester Hydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor); D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate; C498527:SGPP1 protein, human; C401298:sphingosine-1-phosphate phosphatase; C022649:sphingosine 1-phosphate lyase (aldolase)