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

Amour, Augustin, Knight, C. Graham, English, William R., Webster, Ailsa, Slocombe, Patrick M., Knauper, Vera ORCID: https://orcid.org/0000-0002-3965-9924, 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. 10.1016/S0014-5793(02)03047-8

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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
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	Metalloproteinase, Disintegrin metalloproteinase, ADAM, Tissue inhibitor of metalloproteinases, Membrane-type metalloproteinase.
Publisher:	Elsevier
ISSN:	0014-5793
Last Modified:	27 Oct 2022 10:13
URI:	https://orca.cardiff.ac.uk/id/eprint/69339

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