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

FEBS Letters

Milstien, Sheldon²  Spiegel, Sarah¹  Kleuser, Burkhard¹  Maceyka, Michael³ 

[1] Institut fur Pharmazie der Freien Universitat Berlin, Berlin, Germany;Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, MD 20892, USA;Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, W226A New Research Building, 3970 Reservoir Road NW, Washington, DC 20007, USA

关键词: Nuclear sphingosine kinase;    Sphingosine;    Sphingosine-1-phosphate;    BSA;    bovine serum albumin;    PBS;    phosphate-buffered saline;    PDGF;    platelet-derived growth factor;    SPHK;    sphingosine kinase;    SPP;    sphingosine-1-phosphate;   

DOI  :  10.1016/S0014-5793(01)02697-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Subcellular fractionation revealed that a significant fraction of total sphingosine kinase, the enzyme that phosphorylates sphingosine to form the bioactive lipid metabolite sphingosine-1-phosphate, resides in the nuclei of Swiss 3T3 cells, localized to both the nuclear envelope and the nucleoplasm. Platelet-derived growth factor, in addition to rapidly stimulating cytosolic sphingosine kinase, also induced a large increase in nucleoplasm-associated 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 fluorescent protein fusion protein to the nuclear envelope. Our results add sphingosine kinase to the growing list of lipid-metabolizing enzymes associated with the nucleus, and suggest that sphingosine-1-phosphate may also play a role in signal transduction in the nucleus.

【 授权许可】

Unknown