Sphingolipids in Disease

Volume 216 of the series Handbook of Experimental Pharmacology pp 275-303


Regulation of the Sphingosine Kinase/Sphingosine 1-Phosphate Pathway

  • K. Alexa Orr GandyAffiliated withThe Department of Molecular and Cellular Biology and Pathobiology, The Medical University of South Carolina
  • , Lina M. ObeidAffiliated withThe Department of Medicine, Health Science Center, Stony Brook UniversityThe Northport VA Medical Center Email author 

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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.


sphingolipids growth factors epidermal growth factor (EGF) platelet derived growth factor (PDGF) tumor necrosis-α (TNFα) cytokines interleukin tumor growth factor-β (TGFβ) hormones