Sphingosine 1-phosphate and lysophosphatidic acid receptors: agonist and antagonist binding and progress toward development of receptor-specific ligands

Semin Cell Dev Biol. 2004 Oct;15(5):467-76. doi: 10.1016/j.semcdb.2004.05.006.


Sphingosine 1-phosphate and lysophosphatidic acid are two phospholipid growth factors whose importance in physiology and pathophysiology is becoming more and more apparent. Structure-activity relationships for agonism and antagonism at the thirteen known cell-surface and one intracellular receptor are described. Particular emphasis is placed on ligands having different selectivity than the parent molecules. Structural insights regarding agonist and antagonist recognition by the receptors from both computational modeling studies and crystallography are also discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Ligands
  • PPAR gamma / metabolism
  • Protein Binding
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Lysophosphatidic Acid / agonists*
  • Receptors, Lysophosphatidic Acid / antagonists & inhibitors*
  • Receptors, Lysosphingolipid / agonists*
  • Receptors, Lysosphingolipid / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Ligands
  • PPAR gamma
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid
  • Receptors, Lysosphingolipid