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First published online 27 May 2008
doi: 10.1242/jcs.025817

Journal of Cell Science 121, 2054-2061 (2008)
Published by The Company of Biologists 2008
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Research Article

p190B RhoGAP regulates endothelial-cell-associated proteolysis through MT1-MMP and MMP2

Fabien Guegan1,2, Florence Tatin1,2, Thierry Leste-Lasserre1,3, Guillaume Drutel1,3, Elisabeth Genot1,2,4 and Violaine Moreau1,2,4,*

1 Institut Européen de Chimie-Biologie, 2 rue Robert Escarpit, 33600 Pessac, France
2 INSERM, U441, Université Victor Segalen Bordeaux 2, Avenue du Haut-Lévêque, 33600 Pessac, France
3 INSERM, U862, Institut François Magendie, 146 Rue Léo Saignat, 33077 Bordeaux Cedex, France
4 INSERM, U889, Université Victor Segalen Bordeaux 2, 146 Rue Léo Saignat, 33076 Bordeaux, France

* Author for correspondence (e-mail: violaine.moreau{at}inserm.fr)

Accepted 10 April 2008

The two isoforms of p190 RhoGAP (p190A and p190B) are important regulators of RhoGTPase activity in mammalian cells. Both proteins are ubiquitously expressed, are involved in the same signalling pathways and interact with the same identified binding partners. In search of isoform functional specificity, we knocked down the expression of each p190 protein using siRNA and examined the resulting phenotypic changes in human umbilical vein endothelial cells (HUVECs). We provide evidence that p190B plays a crucial role in the regulation of MT1-MMP expression and cell-surface presentation, as well as subsequent MMP2 activation. p190B is involved in both local extracellular matrix degradation at podosomes and endothelial cell assembly into tube-like structures in Matrigel. In addition, whereas p190B knockdown does not affect podosome formation, p190A knockdown increases the number of cells showing podosome structures in HUVECs. We conclude that the two p190 RhoGAP isoforms play distinct roles in endothelial cells. In addition, our data reveal an unsuspected role for p190B in the expression of the two collaborative proteases MT1-MMP and MMP2, thereby affecting matrix remodelling and angiogenesis.

Key words: p190 RhoGAP, Metalloproteinase, Podosomes


Related articles in JCS:

p190A and p190B: not created equal

JCS 2008 121: 1201. [Full Text]  





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