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An update on sphingosine-1-phosphate and other sphingolipid mediators

Nature Chemical Biology volume 6, pages 489–497 (2010)Cite this article

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An Erratum to this article was published on 01 September 2010

This article has been updated

Abstract

Sphingolipids comprise a complex family of naturally occurring molecules that are enriched in lipid rafts and contribute to their unique biochemical properties. Membrane sphingolipids also serve as a reservoir for bioactive metabolites including sphingosine, ceramide, sphingosine-1-phosphate and ceramide-1-phosphate. Among these, sphingosine-1-phosphate has emerged as a central regulator of mammalian biology. Sphingosine-1-phosphate is essential for mammalian brain and cardiac development and for maturation of the systemic circulatory system and lymphatics. In addition, sphingosine-1-phosphate contributes to trafficking and effector functions of lymphocytes and other hematopoietic cells and protects against various forms of tissue injury. However, sphingosine-1-phosphate is also an oncogenic lipid that promotes tumor growth and progression. Recent preclinical and clinical investigations using pharmacological agents that target sphingosine-1-phosphate, its receptors and the enzymes required for its biosynthesis and degradation demonstrate the promise and potential risks of modulating sphingosine-1-phosphate signaling in treatment strategies for autoimmunity, cancer, cardiovascular disease and other pathological conditions.

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Figure 1: The sphingolipid metabolic pathway.
Figure 2: Sphingodynamics.
Figure 3: S1P signaling in the nucleus.
Figure 4: S1P signaling in immunity and tissue injury.

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Change history

  • 20 July 2010

    In the version of this article initially published, the DNA molecule and the SphK2 protein shape were missing from Figure 3. The errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

This work was supported by US National Institutes of Health Public Health Service grants CA77528, CA129438, RAT005336 and GM66954 (J.D.S.). We thank B. Oskouian for careful review of the manuscript.

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    Henrik Fyrst & Julie D Saba

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Fyrst, H., Saba, J. An update on sphingosine-1-phosphate and other sphingolipid mediators. Nat Chem Biol 6, 489–497 (2010). https://doi.org/10.1038/nchembio.392

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