Reference : Regulation of membrane-type 1 matrix metalloproteinase activity by vacuolar H+-ATPases
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/12352
Regulation of membrane-type 1 matrix metalloproteinase activity by vacuolar H+-ATPases
English
Maquoi, Erik mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Peyrollier, K. [> > > >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
Frankenne, Francis [ > > ]
1-Jul-2003
Biochemical Journal
Portland Press
373
Pt 1
19-24
Yes (verified by ORBi)
International
0264-6021
1470-8728
London
United Kingdom
[en] internalization ; matrix metalloproteinase 2 (MMP-2) ; proteinase ; proteinase inhibitor ; tissue inhibitor of matrix metalloproteinases ; 2 (TIMP-2) ; tumour cell
[en] Membrane-type I matrix metalloprotemase (MT1-MMP) is a key enzyme in normal development and malignant processes. The regulation of MT1-MMP activity on the cell surface is a complex process involving autocatalytic processing, tissue inhibitor of MMPs (TIMP) binding and constitutive internalization. However, the fate of internalized MT1-MMP is not known. Acidification of intracellular vacuolar compartments is essential for membrane trafficking, protein sorting and degradation. This acidification is controlled by vacuolar H+-ATPases, which can be selectively inhibited by bafilomycin-A(1). Here, we treated human tumour cell lines expressing MT1-MMP with bafilomycin-A(1), and analysed its effects on MT1-MMP activity, internalization and processing. We show that the activity of MT1-MMP on the cell surface is constitutively down-regulated through a vacuolar HI-ATPase-dependent degradation process. Blockade of this degradation caused the accumulation of TIMP-free active MT1-MMP molecules on the cell surface, although internalization was not affected. As a consequence of this impaired degradation, pro-MMP-2 activation was strongly enhanced. This study demonstrates that the catalytic activity of MT1-MMP on the cell surface is regulated through a vacuolar H+-ATPase-dependent degradation process.
http://hdl.handle.net/2268/12352
10.1042/BJ20030170

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