Sphingosine-1-phosphate induces the association of membrane-type 1 matrix metalloproteinase with p130Cas in endothelial cells |
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Authors: | Gingras Denis Michaud Marisol Di Tomasso Geneviève Béliveau Eric Nyalendo Carine Béliveau Richard |
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Institution: | Laboratoire de Médecine Moléculaire, H?pital Ste-Justine-Université du Québec à Montréal, Centre de Cancérologie Charles-Bruneau, 3175 Chemin C?te-Ste-Catherine, Montréal, Québec, Canada H3T 1C5. |
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Abstract: | 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. |
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Keywords: | EC endothelial cell ECM extracellular matrix HUVEC human umbilical vein endothelial cell MT-MMP membrane-type matrix metalloproteinase S1P sphingosine-1-phosphate |
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