Figure 1.

S1P metabolism and signaling. S1P is produced from sphingosine via SK1 or SK2 and degraded reversibly by one of the SPPs or irreversibly by SPL. Intracellularly, S1P can bind and affect the activity of different targets including BACE1, PPARγ, PHB2, hTERT, and HDAC1/2. S1P can be also secreted from the cells via ABC transporter or Spns2. Extracellular S1P binds to one of its 5 G-protein coupled receptors inducing the activation of distinct G proteins depending on the receptor, the cell type, and the state. Accordingly, extracellular S1P can activate different pathways including Rho, PLC/PKC, PI3K/Akt, and Ras/ERK pathways, thus affecting cell survival, proliferation, motility, and metabolism. S1P: sphingosine-1-phosphate, SK1/2: sphingosine kinase 1/2, SPL: S1P lyase, SPP: S1P phosphatase, BACE1: β-site amyloid precursor protein cleaving enzyme-1, PPARγ: peroxisome proliferator-activated receptor γ, PHB2: Prohibitin 2, hTERT: human telomerase reverse transcriptase, HDAC1/2: Histone Deacetylase 1/2, PLC: phospholipase C, PKC: protein kinase C, PI3K: Phosphoinositol-3-phosphate, ERK: extracellular signal-regulated kinase, S1PR: S1P receptor, Spns2: Spinster 2, cAMP: cyclic adenosine monophosphate.