title: Rho GTPases mediated integrin alpha v beta 3 activation in sphingosine-1-phosphate stimulated chemotaxis of endothelial cells.
abstract: Integrins, a family of transmembrane heterodimeric polypeptides, mediate various biological responses including cell adhesion and migration. In this report, we show that sphingosine-1-phosphate (S1P) activates integrin alpha v beta 3 in endothelial cells (ECs) via the sphingosine-1-phosphate receptor subtype 1 (S1P1)-mediated signaling pathway. S1P treatment results in the activation of integrin alpha v beta 3 in the lamellipodia region of ECs, suggesting that integrin alpha v beta 3 plays a critical role in the S1P-stimulated chemotactic response of ECs. Indeed, S1P treatment induces the association of focal adhesion kinase (FAK) and cytoskeletal proteins with integrin alpha v beta 3, the ligation of alpha v and beta 3 subunits, as well as enhances endothelial migration on vitronectin-coated substrata. Knockdown endothelial S1P1 receptor, treatments with pertussis toxin or dominant-negative-Rho family GTPases abrogates the S1P-induced integrin alpha v beta 3 activation in ECs. Consequently, these treatments markedly inhibit the S1P-induced endothelial migratory response on vitronectin-coated substrata. Collectively, these data indicate that the S1P-mediated signaling via the S1P1/Gi/Rho GTPases pathway activates integrin alpha v beta 3, which is indispensable for S1P-stimulated chemotactic response of ECs.
authors.affiliation: Gheens Center on Aging, Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Jen-Fu
authors.initials: JF
authors.lastname: Lee
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
authors.forename: Menq-Jer
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D015151:Immunoblotting; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019096:Vitronectin / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D039302:Integrin alphaVbeta3; D008246:Lysophospholipids; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D049349:Receptors, Lysosphingolipid; D019096:Vitronectin; C060506:sphingosine 1-phosphate; D037342:Pertussis Toxin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020741:rho GTP-Binding Proteins; D013110:Sphingosine