title: Regulation of the sphingosine kinase/sphingosine 1-phosphate pathway.
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.
authors.affiliation: The Department of Molecular and Cellular Biology and Pathobiology, The Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: K Alexa Orr
authors.initials: KA
authors.lastname: Gandy
authors.forename: Lina M
authors.initials: LM
authors.lastname: Obeid
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate