| Title | Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. |
| Publication Type | Journal Article |
| Year of Publication | 2001 |
| Authors | Lee MJ, Thangada S, Paik JH, Sapkota GP, Ancellin N, Chae SS, Wu M, Morales-Ruiz M, Sessa WC, Alessi DR, Hla T |
| Journal | Mol Cell |
| Volume | 8 |
| Issue | 3 |
| Pagination | 693-704 |
| Date Published | 2001 Sep |
| ISSN | 1097-2765 |
| Keywords | Actins, Animals, Cell Line, Chemotaxis, Endothelium, Vascular, Enzyme Activation, Humans, Immediate-Early Proteins, Lysophospholipids, Models, Biological, Neovascularization, Physiologic, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, rac GTP-Binding Proteins, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Receptors, Lysophospholipid, Recombinant Fusion Proteins, Signal Transduction, Sphingosine |
| Abstract | The role of the protein kinase Akt in cell migration is incompletely understood. Here we show that sphingosine-1-phosphate (S1P)-induced endothelial cell migration requires the Akt-mediated phosphorylation of the G protein-coupled receptor (GPCR) EDG-1. Activated Akt binds to EDG-1 and phosphorylates the third intracellular loop at the T(236) residue. Transactivation of EDG-1 by Akt is not required for G(i)-dependent signaling but is indispensable for Rac activation, cortical actin assembly, and chemotaxis. Indeed, T236AEDG-1 mutant sequestered Akt and acted as a dominant-negative GPCR to inhibit S1P-induced Rac activation, chemotaxis, and angiogenesis. Transactivation of GPCRs by Akt may constitute a specificity switch to integrate rapid G protein-dependent signals into long-term cellular phenomena such as cell migration. |
| DOI | 10.1016/s1097-2765(01)00324-0 |
| Alternate Journal | Mol Cell |
| PubMed ID | 11583630 |
| Grant List | DK45659 / DK / NIDDK NIH HHS / United States HL61371 / HL / NHLBI NIH HHS / United States |
Related Faculty:
Ji-Hye Paik, Ph.D.