Pleiotropic actions of sphingosine-1-phosphate

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that regulates diverse cellular responses including, growth, survival, cytoskeleton rearrangements and movement. S1P plays an important role during development, particularly in vascular maturation and has been implicated in pathophysiology of cancer, wound healing, and atherosclerosis. This review summarizes the evidence showing that signaling induced by S1P is complex and involves both intracellular and extracellular actions. The intracellular effects of S1P remain speculative awaiting the identification of specific targets whereas the extracellular effects of S1P are clearly mediated through the activation of five specific G protein coupled receptors, called SIP1-5. Recent studies demonstrate that intracellular generated S1P can act in a paracrine or autocrine manner to activate its cell surface receptors. (C) 2003 Elsevier Science Ltd. All rights reserved.