Sphingosine-l-phosphate is synthesized by two sphingosine kinases, cytosolic SK1 and nuclear SK2 but SK2 expression was much higher than SK1 in 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 SIP 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 sug- gested 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. (C) 2018 Elsevier Inc. All rights reserved.