Sphingosin1phosphat

Sphingosine-1-phosphate (S1P), sometimes referred to as sphingosin-1-phosphat, is a bioactive sphingolipid metabolite that functions as a signaling molecule in animals. It is produced by the phosphorylation of sphingosine by the kinases SphK1 and SphK2 and is degraded by S1P phosphatases (SPP1/2) and by S1P lyase (SGPL1). S1P forms concentration gradients, with relatively high levels in blood and lymph and lower levels in tissues, enabling directional signaling.

S1P is exported from cells by transporters such as SPNS2 and is carried in the circulation by binding to carrier proteins, including albumin and HDL-associated apolipoprotein M (ApoM). This association helps protect S1P and facilitates its delivery to distant targets.

S1P signals mainly through a family of five G protein–coupled receptors, S1PR1 to S1PR5. Receptor engagement couples to multiple G proteins (Gi, Gq, G12/13) and activates downstream pathways such as PI3K/AKT, MAPK, and Rho family signaling, influencing cell survival, proliferation, cytoskeletal organization, and chemotaxis.

Physiological roles include regulation of immune cell trafficking, particularly the egress of lymphocytes from lymphoid organs; maintenance of vascular integrity and endothelial barrier function; angiogenesis and tissue repair; and modulation of inflammation and contributions to cardiac and nervous system functions. Dysregulation of S1P signaling is implicated in autoimmune diseases, cancer, and fibrotic disorders.

Therapeutically, the orally active prodrug fingolimod (FTY720) is phosphorylated to a functional S1P receptor modulator used to treat multiple sclerosis. Other S1P receptor modulators are under development for various indications. Analytical measurement of S1P in biological samples is commonly performed by LC-MS/MS.