QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

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

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.025817v1 121/12/2054    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guegan, F. Articles by Moreau, V. Search for Related Content PubMed PubMed Citation Articles by Guegan, F. Articles by Moreau, V. Social Bookmarking                         What's this?

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

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

p190A and p190B: not created equal

JCS 2008 121: 1201. [Full Text]  

This article has been cited by other articles:

				S. Linder Invadosomes at a glance J. Cell Sci., September 1, 2009; 122(17): 3009 - 3013. [Full Text] [PDF]

				G. P. van Nieuw Amerongen and V. W. M. van Hinsbergh Role of ROCK I/II in vascular branching Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H903 - H905. [Full Text] [PDF]