Sphingoid bases and phospholipase D activation |
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Authors: | Sarah Spiegel and Sheldon Milstien |
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Affiliation: | a Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, 357 Basic Science Building, 3900 Reservoir Road NW, Washington, DC 20007, USA b Laboratory of Cell Biology, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA |
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Abstract: | There is increased interest in physiological functions and mechanisms of action of sphingolipids metabolites, ceramide, sphingosine, and sphingosine-l-phosphate (SPP), members of a new class of lipid second messengers. This review summarizes current knowledge regarding the role of these sphingolipids metabolites in the actions of growth factors and focuses on the second messenger roles of sphingosine and its metabolite, SPP, in the regulation of cell growth. We also discuss possible interactions with intermediates of the well known glycerophospholipid cycle. Sphingosine and SPP generally provide positive mitogenic signals whereas ceramide has been reported to induce apoptosis and cell arrest in several mammalian cell lines. Stimulation of phospholipase D leading to an increase in phosphatidic acid, a positive regulator of cell growth, by sphingosine and SPP, and its inhibition by ceramide, might be related to their opposite effects on cell growth. This also indicates that sphingolipid turnover could regulate the diacylglycerol cycle. Cross-talk between sphingolipid turnover pathways and the diacylglycerol cycle increases complexity of signaling pathways leading to cellular proliferation and adds additional sites of regulation. |
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Keywords: | Phosphatidic acid Sphingolipids metabolites, Signal transduction |
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