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Sphingolipids in Disease pp 275–303Cite as

Regulation of the Sphingosine Kinase/Sphingosine 1-Phosphate Pathway

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 216))

Abstract

Sphingolipids have emerged as pleiotropic signaling molecules with roles in numerous cellular and biological functions. Defining the regulatory mechanisms governing sphingolipid metabolism is crucial in order to develop a complete understanding of the biological functions of sphingolipid metabolites. The sphingosine kinase/ sphingosine 1-phosphate pathway was originally thought to function in the irreversible breakdown of sphingoid bases; however, in the last few decades it has materialized as an extremely important signaling pathway involved in a plethora of cellular events contributing to both normal and pathophysiological events. Recognition of the SK/S1P pathway as a second messaging system has aided in the identification of many mechanisms of its regulation; however, a cohesive, global understanding of the regulatory mechanisms controlling the SK/S1P pathway is lacking. In this chapter, the role of the SK/S1P pathway as a second messenger is discussed, and its role in mediating TNF-α- and EGF-induced biologies is examined. This work provides a comprehensive look into the roles and regulation of the sphingosine kinase/ sphingosine 1-phosphate pathway and highlights the potential of the pathway as a therapeutic target.

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Funding

This manuscript is based upon work supported in part by a MERIT Award [BX000156-01A1] (LMO) by the Office of Research and Development, Department of Veterans Affairs, Northport VA Medical Center, Northport, NY. The content of this material does not represent the views of the Department of Veterans Affairs or the United States Government, US Department of Education Graduate Assistance in Areas of National Need (GAANN) in Lipid Biology and New Technologies [P200A070596] (KAOG), and National Cancer Institute [PO1-CA97132 (LMO)] and National Institutes of Health National Institute of General Medical Sciences [R01-GM062887 (LMO)].

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Authors and Affiliations

  1. The Department of Molecular and Cellular Biology and Pathobiology, The Medical University of South Carolina, Charleston, SC, 29425, USA

    K. Alexa Orr Gandy

  2. The Department of Medicine, Health Science Center, Stony Brook University, L-4, 179, Stony Brook, NY, 11794-8430, USA

    Lina M. Obeid

  3. The Northport VA Medical Center, Northport, NY, 11768, USA

    Lina M. Obeid

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  1. K. Alexa Orr Gandy
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  2. Lina M. Obeid
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Correspondence to Lina M. Obeid .

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  1. , Department of Molecular Biology, University of Duisburg-Essen, Hufelandstraße 55, Essen, 45122, Germany

    Erich Gulbins

  2. Division of Pulmonary, Allergy, Critical, Department of Medicine, Indiana University School of Medicine, W. Walnut Street 980, Indianapolis, 46202, Indiana, USA

    Irina Petrache

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Gandy, K.A.O., Obeid, L.M. (2013). Regulation of the Sphingosine Kinase/Sphingosine 1-Phosphate Pathway. In: Gulbins, E., Petrache, I. (eds) Sphingolipids in Disease. Handbook of Experimental Pharmacology, vol 216. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1511-4_14

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