Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy

  • Posted on: 1 June 2015
  • By: fcoldren
TitleEmerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy
Publication TypeJournal Article
Year of Publication2015
AuthorsProia RL, Hla T
JournalJ Clin Invest
Date Published2015 Apr

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.

Alternate JournalJ. Clin. Invest.
PubMed ID25831442
PubMed Central IDPMC4409021
Grant ListCA77839 / 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