EDG-1, encoded by the endothelial differentiation gene-1, is a heterotrimeric 
guanine nucleotide binding protein-coupled receptor (GPCR) for 
sphingosine-1-phosphate (SPP) that has been shown to stimulate angiogenesis and 
cell migration in cultured endothelial cells. Unexpectedly, EDG-1 knockout 
embryos had a normal blood vessel network, vasculogenesis and angiogenesis, but 
died in utero owing to massive haemorrhaging as a result of failure of smooth 
muscle cells and pericytes to migrate around the circumference and reinforce 
endothelial tubes [Liu, Wada, Yamashita, Mi, Deng, Hobson, Rosenfeldt, Nava, 
Chae, Lee, et al. (2000) J. Clin. Invest. 106, 951-961]. This vascular 
maturation defect is similar to the phenotype of mice homozygous for disrupted 
alleles of platelet-derived growth factor B-subunit homodimer (PDGF-BB) or its 
receptor PDGFR-beta. We found that fibroblasts from EDG-1 null embryos did not 
migrate toward PDGF or SPP, and inhibition of motility correlated with defective 
activation of the small guanosine triphosphatase Rac, which is required for 
lamellipodia formation and directional locomotion [Hobson, Rosenfeldt, Barak, 
Olivera, Poulton, Caron, Milstien, and Spiegel (2001) Science 291, 1800-1803]. 
Moreover, we showed that PDGF-directed cell migration requires both sphingosine 
kinase activation and expression of EDG-1, suggesting a functional link between 
PDGF signalling and EDG-1. Indeed, treatment of wild-type cells with PDGF 
transactivated EDG-1 as determined by translocation of beta-arrestin and 
phosphorylation of EDG-1. These findings reveal a new paradigm for receptor 
cross-communication in which activation of a GPCR by a receptor tyrosine kinase 
is critical for cell motility. Our observations might also clarify the role of 
EDG-1 in vascular maturation and angiogenesis.