Activation of sphingosine kinase 1

Abstract

Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that regulates many important biological processes as a ligand for cell surface receptors and as an intracellular second messenger. S1P levels inside cells are regulated in a temporal and spatial manner by the balance between its formation, catalyzed by two sphingosine kinase isoenzymes, SphK1 and SphK2, and degradation by S1P lyase and S1P-specific phosphatases. Activation of SphK1 is a key step in the agonist-induced regulation of S1P levels. SphK1 is a cytosolic enzyme and a growing body of evidence suggests that S1P production is also regulated by the translocation of SphK1 to membranes, where its substrate sphingosine is formed. SphK1 translocation to membranes can be mediated by interactions with lipids and proteins. Here we review the current knowledge of SphK1 activation and translocation. © Springer-Verlag Tokyo 2006. All rights reserved.