Figure 2.

Complexity of SphK-S1P “inside-outside” signaling. SphK is a lipid enzyme catalyzing the phosphorylation sphingosine to its active form S1P. S1P can act in an autocrine or paracrine manner. S1P is exported extracellularly through the ABC [106] and Spns2 (Sphingolipid Transporter 2) transporter [107,108] transmembrane proteins or can act intracellularly on yet unknown targets. S1P extracellularly activity occurs through the binding of one or more S1P receptors (S1P1-5) located on the plasma membrane, which are coupled to different internal G proteins which in turn activate or inhibit downstream signaling pathways. This complex S1P signaling paradigm extends the repertoire of diverse cellular and biological processes of the SphK family of lipid isozymes and isoforms.