Sphingosine-1-phosphate receptors: receptor specificity versus functional redundancy

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that has recently been shown to bind cell surface S1P receptors (previously called endothelial differentiation gene (Edg) receptors), which are members of the G-protein-coupled family of receptors. Signaling via S1P is a complex process, as cells usually express a number of these receptors on their surfaces. Many of the S1P receptors share common G-proteins, invoking the question of how these receptors are specific in their actions. This review describes the coupling pathways of S1P receptors, and highlights the in vitro and in vivo evidence for the "uniqueness" of each receptor in activating downstream signaling pathways, taking the effect of S1P on migration as an example.