Article (Scientific journals)
Regulation of membrane-type 1 matrix metalloproteinase activity by vacuolar H+-ATPases
Maquoi, Erik; Peyrollier, K.; Noël, Agnès et al.
2003In Biochemical Journal, 373 (Pt 1), p. 19-24
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Keywords :
internalization; matrix metalloproteinase 2 (MMP-2); proteinase; proteinase inhibitor; tissue inhibitor of matrix metalloproteinases; 2 (TIMP-2); tumour cell
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Maquoi, Erik  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Peyrollier, K.
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Frankenne, Francis
Language :
English
Title :
Regulation of membrane-type 1 matrix metalloproteinase activity by vacuolar H+-ATPases
Publication date :
01 July 2003
Journal title :
Biochemical Journal
ISSN :
0264-6021
eISSN :
1470-8728
Publisher :
Portland Press, London, United Kingdom
Volume :
373
Issue :
Pt 1
Pages :
19-24
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 07 May 2009

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