Vascular endothelial cell migration is regulated in part by the bioactive lipid sphingosine 1-phosphate (S1P), which acts through the G protein-coupled receptor EDG-1. Lee et al. propose that EDG-1 may stimulate cell mobility by inducing the long-term cellular changes that commit cells to chemotaxis. Stimulation of endothelial cells with S1P induced the phosphorylation of the cytoplasmic protein kinase AKT and its subsequent association with EDG-1. Phosphorylation of a critical threonine residue in EDG-1 by AKT was required for EDG-1 to stimulate the assembly of cortical actin and chemotaxis. However, this modification was not required for rapid EDG-1-mediated signaling responses including intracellular calcium mobilization. Phosphorylation of the receptor by AKT may serve as a switch for EDG-1 to make the transition from rapid cellular responses to those that regulate motility.
M.-J. Lee, S. Thangada, J.-H. Paik, G. P. Sapkota, N. Ancellin, S.-S. Chae, M. Wu, M. Morales-Ruiz, W .C. Sessa, D. R. Alessi, T. Hla, Akt-meditaed phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Mol. Cell 8, 693-704 (2001). [Online Journal]