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Concept
Sphingosine-1-phosphate
Summary
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine.
S1P is formed from ceramide, which is composed of a sphingosine and a fatty acid. Ceramidase, an enzyme primarily present in plasma membrane, will convert ceramide to sphingosine. sphingosine is then phosphorylated by sphingosine kinase (SK) isoenzymes. There are two identified isoenzymes, SK1 and SK2. These two enzymes have different tissue distribution. SK1 is highly expressed in spleen, lung and leukocytes, while SK2 is highly expressed in liver and kidney. SK2 is located mainly in the mitochondria, nucleus and the endoplasmic reticulum whereas SK1 is mainly located in cytoplasm and the cell membrane.
S1P can be dephosphorylated to sphingosine by sphingosine phosphatases and can be irreversibly degraded by an enzyme, sphingosine phosphate lyase.
S1P is a blood borne lipid mediator, in particular in association with lipoproteins such as high density lipoprotein (HDL). It is less abundant in tissue fluids. This is referred to as the S1P gradient, which seems to have biological significance in immune cell trafficking.
Originally thought as an intracellular second messenger, it was discovered to be an extracellular ligand for G protein-coupled receptor S1PR1 in 1998. It is now known that sphingosine-1-phosphate receptors (S1P receptors) are members of the lysophospholipid receptor family. There are five described to date. Most of the biological effects of S1P are mediated by signaling through the cell surface receptors.
Although S1P is of importance in the entire human body, it is a major regulator of vascular and immune systems. In addition, it might be relevant in the skin. In the vascular system, S1P regulates angiogenesis, vascular stability, and permeability. In the immune system, it is now recognized as a major regulator of trafficking of T- and B-cells.
Official source
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