The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3

Amour, Augustin, Knight, C.Graham, Webster, Ailsa, Slocombe, Patrick M., Stephens, Paul E., Knauper, Vera ORCID: https://orcid.org/0000-0002-3965-9924, Docherty, Andrew J.P. and Murphy, Gillian 2000. The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. FEBS Letters 473 (3) , pp. 275-279. 10.1016/S0014-5793(00)01528-3

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Abstract

A recombinant soluble form of the catalytic domain of human ADAM-10 was expressed as an Fc fusion protein from myeloma cells. The ADAM-10 was catalytically active, cleaving myelin basic protein and peptides based on the previously described ‘metallosheddase’ cleavage sites of tumour necrosis factor α, CD40 ligand and amyloid precursor protein. The myelin basic protein degradation assay was used to demonstrate that hydroxamate inhibitors of matrix metalloproteinases (MMPs) were also inhibitors of ADAM-10. The natural MMP inhibitors, TIMP-2 and TIMP-4 were unable to inhibit ADAM-10, but TIMP-1 and TIMP-3 were inhibitory. Using a quenched fluorescent substrate assay and ADAM-10 we obtained approximate apparent inhibition constants of 0.1 nM (TIMP-1) and 0.9 nM (TIMP-3). The TIMP-1 inhibition of ADAM-10 could therefore prove useful in distinguishing its activity from that of TACE, which is only inhibited by TIMP-3, in cell based assays.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Publisher:	Wiley
ISSN:	1873-3468
Last Modified:	11 Sep 2023 09:27
URI:	https://orca.cardiff.ac.uk/id/eprint/161580

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