TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrix metalloproteinase immobilized on agarose beads.

The Journal of Biological Chemistry
T KinoshitaMotoharu Seiki

Abstract

Membrane-type 1 matrix metalloproteinase (MT1-MMP)/MMP-14 is the activator of progelatinase A (proGelA)/proMMP-2 on the cell surface. However, it was a paradox that a tissue inhibitor of metalloproteinase-2 (TIMP-2), which is an inhibitor of MT1-MMP, is required for proGelA activation by the cells expressing MT1-MMP. In this study, a truncated MT1-MMP having a FLAG-tag sequence at the C terminus (MT1-F) was immobilized onto agarose beads (MT1-F/B) and used to analyze the role of TIMP-2. The proteolytic activity of MT1-F/B against a synthetic peptide substrate was inhibited by TIMP-2 in a dose-dependent manner. In contrast, TIMP-2 promoted the processing of proGelA by MT1-F/B at low concentrations and inhibited it at higher concentrations. TIMP-2 promoted the binding of proGelA to the MT1-F on the beads by forming a trimolecular complex, which was followed by processing of proGelA. A stimulatory effect of TIMP-2 was observed under conditions in which unoccupied MT1-F was still available. Thus, the ternary complex is thought to act as a means to concentrate the substrate to the bead surface and to present it to the neighboring free MT1-F.

References

Aug 1, 1991·Biochemical Society Transactions·H NagaseG Salvesen
Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·H E Van Wart, H Birkedal-Hansen
Oct 1, 1989·Current Opinion in Cell Biology·C M Alexander, Z Werb
Jan 1, 1995·Methods in Enzymology·G Murphy, F Willenbrock
Dec 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·W G Stetler-StevensonD E Kleiner
Jan 1, 1993·Breast Cancer Research and Treatment·K TryggvasonC Pyke
Dec 22, 1995·The Journal of Biological Chemistry·S J AtkinsonG Murphy
Jan 17, 1996·International Journal of Cancer. Journal International Du Cancer·C GillesJ M Foidart
Nov 12, 1996·Biochemical and Biophysical Research Communications·D C GervasiR Fridman
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·H NakaharaW T Chen

❮ Previous
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Citations

Oct 12, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S M Ellerbroek, M S Stack
Jun 22, 2000·International Journal of Cancer. Journal International Du Cancer·K KoR Takahashi
Jun 8, 2001·International Journal of Cancer. Journal International Du Cancer·C SugimotoS Matsukawa
Feb 16, 2000·Biochemical and Biophysical Research Communications·H MiyamoriH Sato
Oct 12, 2000·Biochemical and Biophysical Research Communications·T KoikeA Iguchi
Jan 25, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Maria Honkavuori-ToivolaMarkku Santala
May 26, 2004·Critical Reviews in Oncology/hematology·G KleinE S J M de Bont
Apr 23, 2003·Biochemical and Biophysical Research Communications·Takahisa TakinoHiroshi Sato
Mar 10, 2000·Biochimica Et Biophysica Acta·K BrewH Nagase
Jul 7, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Y A DeClerck
Feb 27, 2003·Critical Reviews in Oncology/hematology·Ian ChauDavid Cunningham
Apr 28, 2000·The International Journal of Biochemistry & Cell Biology·M NguyenC J Jackson
Jul 5, 2008·Nature Protocols·Kazushi Imai, Yasunori Okada
Sep 1, 1999·Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland· Simpson Thompson
Apr 1, 2000·Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland· Simpson Thompson
Mar 13, 2003·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Y-H ParkC K Min
Mar 21, 2001·Biotechnology & Genetic Engineering Reviews·L M BabéB F Schmidt
May 4, 2005·Clinical Evidence·Simon Harding
Sep 24, 2005·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Toshiyuki OkuseKazushi Imai
Apr 6, 1999·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·M Seiki
Jul 23, 1999·Annals of the New York Academy of Sciences·L JonesJ P Neoptolemos
Aug 18, 2012·Advances in Orthopedics·Olimpio GalassoGiorgio Gasparini
Mar 28, 2006·Investigative Ophthalmology & Visual Science·Sharon ElliotScott W Cousins

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