J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.R800008-JLR200 on April 2, 2008

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Journal of Lipid Research, Vol. 49, 1388-1394, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic Review Series: Sphingolipids. Cross-talk at the crossroads of sphingosine-1-phosphate, growth factors, and cytokine signaling*,1

Deborah A. Lebman* and Sarah Spiegel2,{dagger}

* Department of Microbiology and Immunology and Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, VA 23298
{dagger} Department of Molecular Biology, and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298

* This work was supported by National Institutes of Health Grants R01AI-50094 (S.S.), R01CA-61774 (S.S.) and R37GM-043880 (S.S.) and in part by Philip Morris, USA, Inc. and Philip Morris International (D.A.L.).

1 This paper is dedicated to Professor Herbert Carter, whose pioneering work laid the foundation for the field of sphingolipid chemistry.

Published, JLR Papers in Press, April 2, 2008.

2 To whom correspondence should be addressed. e-mail: sspiegel{at}vcu.edu

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that mediates a wide array of biologic effects through its interaction with a family of five G protein-coupled receptors. Cytokines and growth factors interact with this signaling pathway in a variety of ways, including both activation and regulation of the expression of the enzymes that regulate synthesis and degradation of S1P. Not only do many growth factors and cytokines stimulate S1P production, leading to transactivation of S1P receptors, ligation of S1P receptors by S1P can also transactivate growth factor tyrosine kinase receptors and stimulate growth factor and cytokine signaling cascades.XXX This review discusses the mechanisms involved in cross-talk between S1P, cytokines, and growth factors and the impact of that cross-talk on cell signaling and cell biology.

Supplementary key words transforming growth factor beta • sphingosine kinase • G protein-coupled receptor • growth factor receptor

Abbreviations: EGF, epidermal growth factor; GPCR, G protein-coupled receptor; IGF, insulin-like growth factor; IL, interleukin; MAPK, mitogen-activated protein kinase; NF-{kappa}B, nuclear factor kappa B; NGF, nerve growth factor; PDGF, platelet-derived growth factor; PGE2, prostaglandin E2; S1P, sphingosine-1-phosphate; SphK, sphingosine kinase; TGFβ, transforming growth factor beta; TβR, TGFβ receptor; TNF-{alpha}, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor


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