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

RL Proia, T Hla - The Journal of clinical investigation, 2015 - Am Soc Clin Investig
The Journal of clinical investigation, 2015Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation