Sphingosine 1-phosphate and ceramide 1-phosphate: Expanding roles in cell signaling

The phosphorylated sphingolipid metabolites sphingosine I-phosphate (SIP) and ceramide 1-phosphate (C1P) have emerged as potent bioactive agents. Recent studies have begun to define new biological functions for these lipids. Generated by sphingosine kinases and ceramide kinase, they control numerous aspects of cell physiology, including cell survival and mammalian inflammatory responses. Interestingly, SIP is involved in cyclooxygenase-2 induction and C1P is required for the activation and translocation of cPLA(2). This suggests that these two sphingolipid metabolites may act in concert to regulate production of eicosanoids, important inflammatory mediators. Whereas SIP functions mainly via G-protein-coupled receptors, C1P appears to bind directly to targets such as cPLA(2) and protein phosphatase 1/2A. SIP probably also has intracellular targets, and in plants it appears to directly regulate the G protein alpha subunit GPA1.