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Phytosphingosine 1-phosphate: a high affinity ligand for the S1P 4/Edg-6 receptor

Rios Candelore, Mari ; Wright, Michael J ; Tota, Laurie M ; Milligan, James ; Shei, Gan-Ju ; Bergstrom, James D ; Mandala, Suzanne M

Biochemical and Biophysical Research Communications, 2002, Vol.297(3), pp.600-606 [Peer Reviewed Journal]

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  • Title:
    Phytosphingosine 1-phosphate: a high affinity ligand for the S1P 4/Edg-6 receptor
  • Author: Rios Candelore, Mari ; Wright, Michael J ; Tota, Laurie M ; Milligan, James ; Shei, Gan-Ju ; Bergstrom, James D ; Mandala, Suzanne M
  • Description: It has been reported recently that the phosphorylated form of the immunomodulator FTY720 activates sphingosine 1-phosphate G protein-coupled receptors [1,2]. Therefore, understanding the biology of this new class of receptors will be important in clarifying the immunological function of bioactive lysosphingolipid ligands. The S1P4 receptor has generated interest due to its lymphoid tissue distribution. While theS1P4 receptor binds the prototypical ligand, S1P, a survey of other lysosphingolipids demonstrated that 4d-hydroxysphinganine 1-phosphate, more commonly known as phytosphingosine 1-phosphate (PhS1P), binds toS1P4 with higher affinity. Using radiolabeled S1P (S133P), the affinity of PhS1P for theS1P4 receptor is 1.6 nM, while that of S1P is nearly 50-fold lower (119±20 nM). Radiolabeled PhS1P proved to be superior to S133P in routine binding assays due to improved signal-to-noise ratio. The present study demonstrates the utility of a novel radiolabeled probe, PhS133P, for in vitro studies of theS1P4 receptor pharmacology.© 2002 Elsevier Science (USA)
  • Is Part Of: Biochemical and Biophysical Research Communications, 2002, Vol.297(3), pp.600-606
  • Identifier: ISSN: 0006-291X ; E-ISSN: 1090-2104 ; DOI: 10.1016/S0006-291X(02)02237-4
  • Subjects: 4 D-Hydroxysphinganine 1-Phosphate ; Phytosphingosine-1-Phosphate ; Sphingosine-1-Phosphate ; Lysosphingolipids ; G Protein-Coupled Receptor ; Sp 4/Edg-6 ; Biology ; Chemistry ; Anatomy & Physiology
  • Language: English

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