Sphingosine-1-phosphate

Lipidomics Gateway (28 July 2010) [doi:10.1038/lipidmaps.2010.23]

Essential for mammalian development, this bioactive, oncogenic lipid signals through cell-surface receptors and emerging intracellular interactions.

Structure of S1P. Visit sphing-4-enine-1-phosphate in the LIPID MAPS structure database for more molecular information

Sphingosine-1-phosphate (S1P), systematic name sphing-4-enine-1-phosphate, is generated from sphingosine by either of the two sphingosine kinase enzymes, SPHK1 and SPHK2. The phosphorylation is reversed by S1P phosphatase enzymes, and S1P can be irreversibly degraded by S1P lyase. One of several bioactive sphingolipid metabolites, S1P forms part of a complex signaling network. The multidimensional interplay of sphingolipid metabolism has been dubbed 'sphingodynamics'. ¹

S1P is essential for mammalian development, particularly for maturation of blood vessels. Five cell-surface G protein-coupled receptors, S1P_1–5, specifically mediate S1P signaling. The expression and localization of these determine many of the diverse cellular responses to S1P, which include many pro-survival functions. Accordingly, S1P is implicated in cancer ² . It is also a major regulator of innate and adaptive immunity, influencing hematopoietic cell trafficking and functions. A compound that modulates S1P receptor functions, FTY70, is being investigated as a treatment for autoimmune diseases including multiple sclerosis. ^{1 3}

In common with lysophosphatidic acid, S1P is soluble in lipid membranes and aqueous solution. Many of its functions are ascribed to intercellular communication via the S1P receptors. Nevertheless, it has effects on cells that do not express any of the receptors and intracellular roles have long been postulated. Recently, evidence in support of these has emerged. Earlier this year we highlighted how S1P produced by nuclear SPHK2 can influence transcription of target genes by inhibiting histone deacetylases (Lipid signaling: S1P's nuclear program). Now another direct intracellular target has been identified, as we highlight this month in Sphingosine-1-phosphate: Internal protection. Generated in this case by SPHK1, S1P binds to TRAF2, an E3 ligase that participates in the antiapoptotic program initiated by TNF-α signaling.

Related articles:

Lipid metabolism: Orm SPOTS demand
A role for Orm proteins in sphingolipid homeostasis and childhood asthma.

Lipid signaling: S1P's nuclear program
Sphingosine-1-phosphate binds to and inhibits histone deacetylases 1 and 2, and regulates gene expression.

Phytosphingosine 1-phosphate
Abundant in plants and fungi but also found in animals, this signaling lipid regulates cellular stress responses in yeast.

Sphingosine 1-phosphate signaling: Treg or not Treg, that is the question
S1P1 activates the mTOR-Akt pathway to suppress Treg-cell differentiation and activity.

Fungal toxicity: Based in sphinganine
Ceramide synthases are inhibited by a family of cereal mold toxins, fumonisins, causing accumulation of a novel category of sphingoid base with potential for cell signaling.

Emma Leah