The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs

Amour, Augustin, Knight, C. Graham, English, William R. ORCID: https://orcid.org/0000-0003-3024-2441, Webster, Ailsa, Slocombe, Patrick M., Knäuper, Vera, Docherty, Andrew J. P., Becherer, J. David, Blobel, Carl P. and Murphy, Gillian (2002) The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs. FEBS Letters, 524 (1-3). pp. 154-158. ISSN 0014-5793

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Abstract

The ADAM family of proteases are type I transmembrane proteins with both metalloproteinase and disintegrin containing extracellular domains. ADAMs are implicated in the proteolytic processing of membrane-bound precursors and involved in modulating cell–cell and cell–matrix interactions. ADAM8 (MS2, CD156) has been identified in myeloid and B cells. In this report we demonstrate that soluble ADAM8 is an active metalloprotease in vitro and is able to hydrolyse myelin basic protein and a variety of peptide substrates based on the cleavage sites of membrane-bound cytokines, growth factors and receptors which are known to be processed by metalloproteinases. Interestingly, although ADAM8 was inhibited by a number of peptide analogue hydroxamate inhibitors, it was not inhibited by the tissue inhibitors of metalloproteinases (TIMPs). We also demonstrate that the activity of recombinant soluble ADAM9 (meltrin-γ, MDC9) lacks inhibition by the TIMPs, but can be inhibited by hydroxamate inhibitors. The lack of TIMP inhibition of ADAM8 and 9 contrasts with other membrane-associated metalloproteinases characterised to date in this respect (ADAM10, 12, 17, and the membrane-type metalloproteinases) which have been implicated in protein processing at the cell surface.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	LivePure Connector
Date Deposited:	15 Dec 2022 10:31
Last Modified:	19 Oct 2023 03:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/90200
DOI:	10.1016/S0014-5793(02)03047-8

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