Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility

EDG-1 is a heterotrimeric guanine nucleotide binding protein-coupled recept or (GPCR) for sphingosine-1-phosphate (SPP). Cell migration toward platelet -derived growth factor (PDGF). which stimulates sphingosine kinase and incr eases intracellular SPP, was dependent on expression of EDG-1. Deletion of edg-1 or inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also activation of the small guanosine triphosphatase Rac, which is es sential for protrusion of lamellipodia and forward movement. Moreover, PDGF activated EDG-1, as measured by translocation of beta -arrestin and phosph orylation of EDG-1. Our results reveal a role for receptor cross-communicat ion in which activation of a GPCR by a receptor tyrosine kinase is critical for cell motility.