Export and functions of sphingosine-1-phosphate.
The sphingolipid metabolite, sphingosine-1-phosphate (S1P), has emerged as a critical player in a number of fundamental biological processes and is important in cancer, angiogenesis, wound healing, cardiovascular function, atherosclerosis, immunity and asthma, among others. Activation of sphingosine kinases, enzymes that catalyze the phosphorylation of sphingosine to S1P, by a variety of agonists, including growth factors, cytokines, hormones, and antigen, increases intracellular S1P. Many of the biological effects of S1P are mediated by its binding to five specific G protein-coupled receptors located on the cell surface in an autocrine and/or paracrine manner. Therefore, understanding the mechanism by which intracellularly generated S1P is released out of cells is both interesting and important. In this review, we will discuss how S1P is formed and released. We will focus particularly on the current knowledge of how the S1P gradient between tissues and blood is maintained, and the role of ABC transporters in S1P release.
Kim
Roger H
RH
Division of Surgical Oncology, Department of Surgery and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA.
Takabe
Kazuaki
K
Milstien
Sheldon
S
Spiegel
Sarah
S
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology; D001692:Biological Transport; D008246:Lysophospholipids / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000502:physiology; D000099157:Sphingosine Kinase
D018528:ATP-Binding Cassette Transporters; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D043562:Receptors, G-Protein-Coupled; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate