A splicing isoform of LPP1, LPP1a, exhibits high phosphatase activity toward FTY720 phosphate

Biochem Biophys Res Commun. 2008 Oct 31;375(4):675-9. doi: 10.1016/j.bbrc.2008.07.165. Epub 2008 Aug 26.


The sphingolipid metabolite sphingosine 1-phosphate (S1P) plays an essential function in the egress of T cells from the thymus and secondary lymphoid organs. The novel immunomodulating agent FTY720 is phosphorylated in vivo to the functional form FTY720 phosphate (FTY720-P), which is structurally similar to S1P. FTY720-P inhibits the S1P-mediated T cell egress as an agonist of S1P receptors. FTY720-P is not stable in plasma and is dephosphorylated to FTY720. In the present study, we investigated activities toward FTY720-P of LPP family members (LPP1, LPP1a, LPP2, and LPP3), which exhibit broad substrate specificity. Of the four, LPP1a, the splicing isoform of LPP1, had the highest activity toward FTY720-P, and the highest affinity. Among blood-facing cells tested, only endothelial cells displayed high phosphatase activity for FTY720-P. Significant levels of LPP1a expression were found in endothelial cells, suggesting that LPP1a is important for the dephosphorylation of FTY720-P in plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Endothelial Cells / enzymology*
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppressive Agents / metabolism*
  • Phosphatidate Phosphatase / genetics
  • Phosphatidate Phosphatase / metabolism*
  • Propylene Glycols / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism


  • Immunosuppressive Agents
  • Propylene Glycols
  • Protein Isoforms
  • lipid phosphate phosphatase
  • Phosphatidate Phosphatase
  • Fingolimod Hydrochloride
  • Sphingosine