Stimulation of nuclear sphingosine kinase activity by platelet-derived growth factor

Subcellular fractionation revealed that a significant fraction of total sph ingosine kinase, the enzyme that phosphorylates sphingosine to form the bio active lipid metabolite sphingosine-1-phosphate, resides in the nuclei of S wiss 3T3 cells, localized to both the nuclear envelope and the nucleoplasm. Platelet-derived growth factor, in addition to rapidly stimulating cytosol ic sphingosine kinase, also induced a large increase in nucleoplasm-associa ted activity after 12-24 h that correlated with progression of cells to the S-phase of the cell cycle and translocation of sphingosine kinase-green fl uorescent protein fusion protein to the nuclear envelope. Our results add s phingosine kinase to the growing list of lipid-metabolizing enzymes associa ted with the nucleus, and suggest that sphingosine-1-phosphate may also pla y a role in signal transduction in the nucleus. (C) 2001 Published by Elsev ier Science B.V. on behalf of the Federation of European Biochemical Societ ies.