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.
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