The Role of Sphingosine-1-Phosphate and Ceramide-1-Phosphate in Inflammation and Cancer

Figure 2

Cellular localization of sphingosine-1-phosphate and ceramide-1-phosphate. ER is the source of ceramide synthesis. Ceramide translocates to the Golgi by ceramide transport protein (CERT) for the synthesis of C1P by Golgi-localized CERK. Ceramide phosphate transfer protein (CPTP) was hypothesized to deliver C1P to the other organelles. Ceramide is produced in the plasma membrane, nucleus, lysosomes, and mitochondria from sphingomyelin (SM). Nuclear CERK can phosphorylate ceramide to form C1P. CERK localization in the mitochondria was not reported. Sphingosine is generated from the ceramide by the ceramidase (CDase) in the plasma membrane, lysosomes, nucleus, and mitochondria. Sphingosine kinase 1 phosphorylates sphingosine to produce sphingosine-1-phosphate (S1P) in the cytosol and plasma membrane for intra- and extracellular signaling. Nuclear and mitochondrial S1P produced from sphingosine by the SphK2 for intracellular signaling.