Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-α convertase activity but does not activate pro-MMP2

English, William R., Puente, Xose S., Freije, José M.P., Knauper, Vera ORCID: https://orcid.org/0000-0002-3965-9924, Amour, Augustin, Merryweather, Ann, López-Otı́n, Carlos and Murphy, Gillian 2000. Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-α convertase activity but does not activate pro-MMP2. Journal of Biological Chemistry 275 (19) , pp. 14046-14055. 10.1074/jbc.275.19.14046

Full text not available from this repository.

Abstract

Membrane type 4 matrix metalloproteinase (MT4-MMP) shows the least sequence homology to the other MT-MMPs, suggesting a distinct function for this protein. We have isolated a complete cDNA corresponding to the mouse homologue which includes the signal peptide and a complete pro-domain, features that were lacking from the human form originally isolated. Mouse MT4-MMP (mMT4-MMP) expressed in COS-7 cells is located at the cell surface but does not show ability to activate pro-MMP2. The pro-catalytic domain was expressed in Escherichia coli as insoluble inclusions and active enzyme recovered after refolding. Activity of the isolated catalytic domain against synthetic peptides commonly used for MMP enzyme assays could be inhibited by TIMP1, -2, and -3. The recombinant mMT4-MMP catalytic domain was also unable to activate pro-MMP2 and was very poor at hydrolyzing components of the extracellular matrix with the exception of fibrinogen and fibrin. mMT4-MMP was able to hydrolyze efficiently a peptide consisting of the pro-tumor necrosis factor α (TNFα) cleavage site, a glutathioneS-transferase-pro-TNFα fusion protein, and was found to shed pro-TNFα when co-transfected in COS-7 cells. MT4-MMP was detected by Western blot in monocyte/macrophage cell lines which in combination with its fibrinolytic and TNFα-converting activity suggests a role in inflammation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Publisher:	Elsevier
ISSN:	0021-9258
Last Modified:	14 Sep 2023 09:42
URI:	https://orca.cardiff.ac.uk/id/eprint/161593

Actions (repository staff only)

Edit Item