Membrane type matrix metalloproteinase 1 activates pro-gelatinase A without furin cleavage of the N-terminal domain.

The Journal of Biological Chemistry
Jian CaoS Zucker

Abstract

Membrane type matrix metalloproteinase 1 (MT-MMP1), a novel 63-kDa member of the matrix metalloproteinase family, is a membrane-anchored enzyme and an activator for gelatinase A. In addition to its C-terminal hydrophobic transmembrane domain, MT-MMP1 has an insertion of 11 amino acids between its propeptide and catalytic domain encrypted with a RRKR recognition motif for the paired basic amino acid cleaving enzyme, furin. In this report, we investigated whether the cleavage of the RRKR motif of MT-MMP1 by Golgi-associated furin is analogous to a similar enzyme activation mechanism observed with stromelysin-3. Mutant forms of MT-MMP1 were cotransfected into COS-1 cells with cDNAs for pro-gelatinase A and/or furin. Immunoprecipitation and immunoblotting using specific antibodies were employed to characterize cell proteins. Whereas furin readily cleaved soluble MT-MMP1 lacking the transmembrane domain (DeltaMT-MMP1), a soluble stromelysin-1/DeltaMT-MMP1 chimera without the RRKR basic motif was resistant to furin-induced cleavage. COS-1 cells cotransfected with wild type MT-MMP1 cDNA and furin cDNA demonstrated a 63-kDa protein (latent enzyme) on SDS-polyacrylamide gel electrophoresis rather than the anticipated lower molecular wei...Continue Reading

References

Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R J WiseR J Kaufman
Jul 15, 1995·The Biochemical Journal·P E MilhietG Boileau
Jan 1, 1993·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·H Birkedal-HansenJ A Engler
Feb 1, 1993·Analytical Biochemistry·F W Kluxen, H Lübbert
Dec 22, 1995·The Journal of Biological Chemistry·S J AtkinsonG Murphy

❮ Previous
Next ❯

Citations

Oct 12, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S M Ellerbroek, M S Stack
Jul 20, 2010·Amino Acids·T Klein, R Bischoff
May 26, 2004·Critical Reviews in Oncology/hematology·G KleinE S J M de Bont
Jun 5, 2002·Molecular and Cellular Endocrinology·Michael F SmithGeorge W Smith
Sep 17, 2002·Current Opinion in Cell Biology·Motoharu Seiki
Dec 5, 1998·The International Journal of Biochemistry & Cell Biology·M Polette, P Birembaut
Sep 15, 2010·The Journal of Biological Chemistry·Antoine DufourJian Cao
Jun 13, 2000·Cancer Biotherapy & Radiopharmaceuticals·I ContastaD Adorno
Nov 16, 2006·Cancer Biotherapy & Radiopharmaceuticals·Patrizia PellegriniDomenico Adorno
Jul 11, 2000·Molecular Biology of the Cell·I Yana, S J Weiss
Sep 15, 2006·Molecular Biology of the Cell·Hyejin LeeJaro Sodek
Nov 13, 1998·Current Opinion in Lipidology·S J George
Nov 5, 1997·European Journal of Biochemistry·V KnäuperG Murphy
Apr 6, 1999·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·G MurphyJ Gavrilovic
Apr 6, 1999·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·M Seiki
Jul 23, 1999·Annals of the New York Academy of Sciences·J CaoS Zucker
May 19, 2012·Journal of Cell Science·Massimiliano BaldassarreDavid A Calderwood
Jan 26, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J AlvarezJ M López
Nov 22, 2011·Molecular Aspects of Medicine·Diego SbardellaMassimo Coletta
Oct 27, 2010·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Niccola FunelNicoletta Gagliano
Aug 3, 2007·Matrix Biology : Journal of the International Society for Matrix Biology·Hyun-Jeong Ra, William C Parks
Jul 19, 2008·Journal of Cellular Physiology·Antoine DufourJian Cao
Feb 21, 2013·The FEBS Journal·Autumn Tocchi, William C Parks
Mar 23, 2005·Biochimie·N E Sounni, A Noel
May 25, 2002·Seminars in Cancer Biology·Sonia Hernandez-BarrantesRafael Fridman
May 31, 2015·Journal of Muscle Research and Cell Motility·C Snyman, C U Niesler
May 25, 2015·Biochemical Pharmacology·Bruno Ramos-MolinaIris Lindberg

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.