The cross roles of sphingosine kinase 1/2 and ceramide glucosyltransferase in cell growth and death

Abstract

Sphingosine-1-phosphate is synthesized by two sphingosine kinases, cytosolic SK1 and nuclear SK2 but SK2 expression was much higher than SK1in mouse skin fibroblasts. However, in SK2−/− cells, SK1 expression was markedly increased to SK2 levels whereas in SK1−/− cells, SK2 expression was unaffected. Ceramide, glucosylceramide and sphingosine levels were all increased in SK1−/− but less so in SK2−/− cells and S1P levels were not significantly reduced in either SK1−/− or SK2−/− cells. Greatly increased Ceramide glucosyltransferase expression was observed in SK1−/− cells but less so in SK2−/− cells suggested a role in drug resistance. SK2−/− cells grew faster than control and SK1−/−. The cell division gene PCNA was significantly overexpressed in SK2−/− cells, suggesting a cross regulation between SKs and Ceramide glucosyltransferase.