Sphingosine‐1‐Phosphate as an Intercellular Signaling Moleculea

Sphingosine-1-phosphate (Sph-1-P) has been implicated as an intracellular second messenger in many studies. Previously, we found the roles of Sph-1-P as a platelet activating lipid released from stimulated platelets and as a lipid regulator of cell motility. We first investigated the mechanism by which Sph-1-P induces activation in platelets. Although exogenous Sph-1-P activated platelets, intracellular Sph-1-P formed from exogenously added Sph failed to do so. Supporting the notion that exogenous Sph-1-P stimulates platelets from outside, we found that contact of platelet surfaces with Sph-1-P-immobilized glass beads resulted in platelet activation. Using these glass beads, we next found that exogenously added Sph-1-P inhibits F10 cell motility from outside through its specific binding site(s) on the cell. We finally identified putative receptor protein(s) for Sph-1-P on the surface of F10 cells.