Sphingosine-1-phosphate induces the association of membrane-type 1 matrix metalloproteinase with p130Cas in endothelial cells.
Membrane-type 1 matrix metalloproteinase (MT1-MMP) plays an important role in sphingosine-1-phosphate(S1P)-dependent migration of endothelial cells but the underlying mechanisms remain largely unknown. Herein, we show that S1P promotes the relocalization of MT1-MMP to peripheral actin-rich membrane ruffles that is coincident with its association with the adaptor protein p130Cas at the leading edge of migrating cells. Immunoprecipitation and confocal microscopy analyses suggest that this interaction required the tyrosine phosphorylation of p130Cas and also involves S1P-dependent phosphorylation of MT1-MMP within its cytoplasmic sequence. The interaction of MT1-MMP with p130Cas at the cell periphery suggests the existence of a close interplay between pericellular proteolysis and signaling pathways involved in EC migration.
Gingras
Denis
D
Laboratoire de Médecine Moléculaire, Hôpital Ste-Justine-Université du Québec à Montréal, Centre de Cancérologie Charles-Bruneau, 3175 Chemin Côte-Ste-Catherine, Montréal, Québec, Canada H3T 1C5.
Michaud
Marisol
M
Di Tomasso
Geneviève
G
Béliveau
Eric
E
Nyalendo
Carine
C
Béliveau
Richard
R
D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014018:Tissue Distribution
D050719:Crk-Associated Substrate Protein; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D011505:Protein-Tyrosine Kinases; D053511:Matrix Metalloproteinase 14; D013110:Sphingosine