The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs. Academic Article uri icon

Overview

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-gamma, 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.

publication date

  • July 31, 2002

Research

keywords

  • Antigens, CD
  • Antigens, Surface
  • Disintegrins
  • Membrane Proteins
  • Metalloendopeptidases
  • Tissue Inhibitor of Metalloproteinases

Identity

Scopus Document Identifier

  • 18444388856

PubMed ID

  • 12135759

Additional Document Info

volume

  • 524

issue

  • 1-3