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

Menq-Jer Lee, Shobha Thangada, Ji-Hye Paik, Gopal P. Sapkota, Nicolas Ancellin, Sung-Suk Chae, Mingtao Wu, Manuel Morales-Ruiz, William C. Sessa, Dario R. Alessi, Timothy Hla

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    256 Citations (Scopus)

    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 T236 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.

    Original languageEnglish
    Pages (from-to)693-704
    Number of pages12
    JournalMolecular Cell
    Volume8
    Issue number3
    DOIs
    Publication statusPublished - Sep 2001

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  • Cite this

    Lee, M-J., Thangada, S., Paik, J-H., Sapkota, G. P., Ancellin, N., Chae, S-S., Wu, M., Morales-Ruiz, M., Sessa, W. C., Alessi, D. R., & Hla, T. (2001). Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Molecular Cell, 8(3), 693-704. https://doi.org/10.1016/S1097-2765(01)00324-0