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

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.