title: An autocrine sphingosine-1-phosphate signaling loop enhances NF-kappaB-activation and survival.
abstract: BACKGROUND
  Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a multitude of cellular functions, including cell proliferation, survival, migration and angiogenesis. S1P mediates its effects either by signaling through G protein-coupled receptors (GPCRs) or through an intracellular mode of action. In this study, we have investigated the mechanism behind S1P-induced survival signalling.
  
  
  RESULTS
  We found that S1P protected cells from FasL-induced cell death in an NF-kappaB dependent manner. NF-kappaB was activated by extracellular S1P via S1P2 receptors and Gi protein signaling. Our study also demonstrates that extracellular S1P stimulates cells to rapidly produce and secrete additional S1P, which can further amplify the NF-kappaB activation.
  
  
  CONCLUSIONS
  We propose a self-amplifying loop of autocrine S1P with capacity to enhance cell survival. The mechanism provides increased understanding of the multifaceted roles of S1P in regulating cell fate during normal development and carcinogenesis.
authors.affiliation: Department of Biology, Abo Akademi University, 20520 Turku, Finland.
authors.forename: Tomas
authors.initials: T
authors.lastname: Blom
authors.forename: Nina
authors.initials: N
authors.lastname: Bergelin
authors.forename: Annika
authors.initials: A
authors.lastname: Meinander
authors.forename: Christoffer
authors.initials: C
authors.lastname: Löf
authors.forename: J Peter
authors.initials: JP
authors.lastname: Slotte
authors.forename: John E
authors.initials: JE
authors.lastname: Eriksson
authors.forename: Kid
authors.initials: K
authors.lastname: Törnquist
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D019898:Autocrine Communication; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D053222:Fas Ligand Protein / Q000378:metabolism; D025461:Feedback, Physiological; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053222:Fas Ligand Protein; D005419:Flavonoids; C471998:JTE 013; D008246:Lysophospholipids; D016328:NF-kappa B; D011720:Pyrazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; C466999:SPHKAP protein, human; C060506:sphingosine 1-phosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013110:Sphingosine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one