Sphingosine kinase 1 is an intracellular effector of phosphatidic acid.
Sphingosine kinase 1 (SK1) phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). Because both substrate and product of the enzyme are potentially important signaling molecules, the regulation of SK1 is of considerable interest. We report that SK1, which is ordinarily a cytosolic enzyme, translocates in vivo and in vitro to membrane compartments enriched in phosphatidic acid (PA), the lipid product of phospholipase D. This translocation depends on direct interaction of SK1 with PA, because recombinant purified enzyme shows strong affinity for pure PA coupled to Affi-Gel. The SK1-PA interaction maps to the C terminus of SK1 and is independent of catalytic activity or of the diacylglycerol kinase-like domain of the enzyme. Thus SK1 constitutes a novel, physiologically relevant PA effector.
Department of Signalling, Babraham Institute, Cambridge CB2 4AT, United Kingdom.
Christine
C
Delon
Maria
M
Manifava
Eleanor
E
Wood
Dawn
D
Thompson
Sonja
S
Krugmann
Susan
S
Pyne
Nicholas T
NT
Ktistakis
D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D019556:COS Cells; D020134:Catalytic Domain; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D019852:Diacylglycerol Kinase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015151:Immunoblotting; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010712:Phosphatidic Acids / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D000099157:Sphingosine Kinase
D019852:Diacylglycerol Kinase; D049452:Green Fluorescent Proteins; D008055:Lipids; D008081:Liposomes; D010712:Phosphatidic Acids; D010739:Phospholipase D; D017853:Phosphotransferases (Alcohol Group Acceptor); D011994:Recombinant Proteins; D000099157:Sphingosine Kinase