Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy
Title | Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Proia RL, Hla T |
Journal | J Clin Invest |
Volume | 125 |
Issue | 4 |
Pagination | 1379-87 |
Date Published | 2015 Apr |
ISSN | 1558-8238 |
Abstract | Membrane sphingolipids are metabolized to sphingosine-1-phosphate (S1P), a bioactive lipid mediator that regulates many processes in vertebrate development, physiology, and pathology. Once exported out of cells by cell-specific transporters, chaperone-bound S1P is spatially compartmentalized in the circulatory system. Extracellular S1P interacts with five GPCRs that are widely expressed and transduce intracellular signals to regulate cellular behavior, such as migration, adhesion, survival, and proliferation. While many organ systems are affected, S1P signaling is essential for vascular development, neurogenesis, and lymphocyte trafficking. Recently, a pharmacological S1P receptor antagonist has won approval to control autoimmune neuroinflammation in multiple sclerosis. The availability of pharmacological tools as well as mouse genetic models has revealed several physiological actions of S1P and begun to shed light on its pathological roles. The unique mode of signaling of this lysophospholipid mediator is providing novel opportunities for therapeutic intervention, with possibilities to target not only GPCRs but also transporters, metabolic enzymes, and chaperones. |
DOI | 10.1172/JCI76369 |
Alternate Journal | J. Clin. Invest. |
PubMed ID | 25831442 |
PubMed Central ID | PMC4409021 |
Grant List | CA77839 / CA / NCI NIH HHS / United States HL117798 / HL / NHLBI NIH HHS / United States HL67330 / HL / NHLBI NIH HHS / United States HL89934 / HL / NHLBI NIH HHS / United States |