title: The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter of the phosphorylated form of the immunomodulating agent FTY720.
abstract: FTY720 is a novel immunomodulating drug that can be phosphorylated inside cells; its phosphorylated form, FTY720-P, binds to a sphingosine 1-phosphate (S1P) receptor, S1P(1), and inhibits lymphocyte egress into the circulating blood. Although the importance of its pharmacological action has been well recognized, little is known about how FTY720-P is released from cells after its phosphorylation inside cells. Previously, we showed that zebrafish Spns2 can act as an S1P exporter from cells and is essential for zebrafish heart formation. Here, we demonstrate that human SPNS2 can transport several S1P analogues, including FTY720-P. Moreover, FTY720-P is transported by SPNS2 through the same pathway as S1P. This is the first identification of an FTY720-P transporter in cells; this finding is important for understanding FTY720 metabolism.
authors.affiliation: Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hisano
authors.forename: Naoki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kawahara
authors.forename: Akihito
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nishi
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011409:Propylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D008565:Membrane Proteins; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine