Sphingosine-1-phosphate signaling regulates lamellipodia localization of cortactin complexes in endothelial cells.

Journal Article (Journal Article)

Sphingosine-1-phosphate (S1P), a serum-borne lipid mediator, was demonstrated to be a potent chemoattractant of endothelial cells. It was recently shown that the colocalization of cortactin and actin related protein 2/3 (Arp2/3) in the lamellipodia is critical to S1P-induced endothelial chemotaxis. In this report, we describe that S1P-stimulated cortactin translocation to the cell periphery to form lamellipodia is specifically mediated by the endothelial S1P1 G-protein coupled receptor, and is regulated by G(i)-mediated Akt-dependent S1P1 receptor phosphorylation and Cdc42/Rac activation pathways. In contrast to Src-dependent fibroblast growth factor-induced cortactin translocation, tyrosine phosphorylation cascades are not required for S1P-mediated lamellipodia formation and chemotaxis. Furthermore, we also demonstrate that S1P signaling, via the G(i)/Akt/S1P1 phosphorylation/Rac pathway, regulates the cortactin-Arp2/3 complex formation, which ultimately results in membrane ruffling, formation of the lamellipodia and endothelial migration.

Full Text

Duke Authors

Cited Authors

  • Lee, J-F; Ozaki, H; Zhan, X; Wang, E; Hla, T; Lee, M-J

Published Date

  • September 2006

Published In

Volume / Issue

  • 126 / 3

Start / End Page

  • 297 - 304

PubMed ID

  • 16416022

International Standard Serial Number (ISSN)

  • 0948-6143

Digital Object Identifier (DOI)

  • 10.1007/s00418-006-0143-z


  • eng

Conference Location

  • Germany