Sphingosine-1-phosphate (d18:1)

Sphingosine-1-phosphate (S1P) is the product of phosphorylation of sphingosine by sphingosine kinase that is secreted from cells and acts as an agonist at S1P receptors.^1,2 It increases intracellular calcium levels in TAg-Jurkat cells expressing S1P₁ and G_qi5, which allows for phospholipase C stimulation by G_i proteins, when used at a concentration of 200 nM, as well as in TAg-Jurkat cells expressing S1P₂ and S1P₃ receptors (EC₅₀s = 8 and 11 nM, respectively).³ Intra- and extracellular levels of S1P vary spatially allowing it to function as an autocrine or paracrine factor, respectively, and dysregulation of S1P levels are associated with various disease states, such as inflammation and autoimmunity.⁴ S1P has a wide variety of effects, including an involvement in cell growth, angiogenesis, immunity, and neuroprotection.

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1. Sanchez, T., and Hla, T. Structural and functional characteristics of S1P receptors. J. Cell. Biochem. 92(5), 913-922 (2004).

2. van Koppen, C.J., zu Heringdorf, D.M., Laser, K.T., et al. Activation of a high affinity Gi protein-coupled plasma membrane receptor by sphingosine-1-phosphate. The Journal of Biological Chemisty 271(4), 2082-2087 (1996).

3. An, S., Bleu, T., and Zheng, Y. Transduction of intracellular calcium signals through G protein-mediated activation of phospholipase C by recombinant sphingosine 1-phosphate receptors. Mol. Pharmacol. 55(5), 787-794 (1999).

4. Cartier, A., and Hla, T. Sphingosine 1-phosphate: Lipid signaling in pathology and therapy. Science 366(6463), (2019).