Regulation of sphingosine kinase and sphingolipid signaling

Abstract

Bioactive sphingolipids, including ceramide, sphingosine and sphingosine 1-phosphate are important regulators of many cellular processes, including cell survival, proliferation, differentiation, migration and immune responses. Although the levels of these bioactive sphingolipids are regulated by complex pathways subject to spatial and temporal control, the sphingosine kinases have emerged as critical central regulators of this system and, as a consequence, they have received substantial recent attention as potential therapeutic targets for cancer and a range of other conditions. Deciphering the molecular mechanisms that regulate both the activity and subcellular localization of these enzymes is vital for understanding the control of bioactive sphingolipid generation and action, and has clear implications for therapeutic strategies targeting these enzymes.