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.{45658,2815} It increases intracellular calcium levels in TAg-Jurkat cells expressing S1P1 and Gqi5, which allows for phospholipase C stimulation by Gi 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).{45659} 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.{45660} S1P has a wide variety of effects, including an involvement in cell growth, angiogenesis, immunity, and neuroprotection.