2. Academic Validation
  3. Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis

Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis

  • Mol Cell. 2001 Sep;8(3):693-704. doi: 10.1016/s1097-2765(01)00324-0.
M J Lee 1,  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
Affiliations

Affiliation

  • 1 Center for Vascular Biology and Department of Physiology, University of Connecticut Health Center, Farmington, CT 06030, USA.
PMID: 11583630 DOI: 10.1016/s1097-2765(01)00324-0
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.

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