Sphingosine-1-phosphate signaling regulates lamellipodia localization of cortactin complexes in endothelial cells |
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Authors: | Jen-Fu Lee Harunobu Ozaki Xi Zhan Eugenia Wang Timothy Hla Menq-Jer Lee |
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Institution: | (1) Gheens Center on Aging, Department of Microbiology and Immunology, University of Louisville Health Science Center, 580 S. Preston St., Louisville, KY 40202, USA;(2) Department of Cardiology, Keihanna hospital, 1-2-1 Fujisakahigashi-cho, 573-0153 Hirakata, Osaka, Japan;(3) Department of Experimental Pathology, Holland Laboratory, American Red Cross, Rockville, MA 20855, USA;(4) Gheens Center on Aging, University of Louisville Health Science Center, Louisville, KY 40202, USA;(5) Center for Vascular Biology, Department of Physiology, University of Connecticut Health Center, Farmington, CT, USA |
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Abstract: | 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 Gi-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 Gi/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.J.F. Lee and H. Ozaki contributed equally to this work |
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Keywords: | S1P signaling S1P1 receptor Cortactin– Arp2/3 Lamellipodia Endothelial chemotaxis |
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