ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitorsq

Juan Carlos Rodríguez-Manzaneque, Jennifer Westling, Shelley N.M. Thai, Alfonso Luque, Vera Knauper, Gillian Murphy, John D. Sandy, M. Luisa Iruela-Arispe

Research output: Contribution to journalArticlepeer-review

207 Scopus citations


ADAMTS1 is a secreted protein that belongs to the recently described ADAMTS (a disintegrin and metalloprotease with thrombospondin repeats) family of proteases. Evaluation of ADAMTS1 catalytic activity on a panel of extracellular matrix proteins showed a restrictive substrate specificity which includes some proteoglycans. Our results demonstrated that human ADAMTS1 cleaves aggrecan at a previously shown site by its mouse homolog, but we have also identified additional cleavage sites that ultimately confirm the classification of this protease as an 'aggrecanase'. Specificity of ADAMTS1 activity was further verified when a point mutation in the zinc-binding domain abolished its catalytic effects, and latency conferred by the prodomain was also demonstrated using a furin cleavage site mutant. Suppression of ADAMTS1 activity was accomplished with a specific monoclonal antibody and some metalloprotease inhibitors, including tissue inhibitor of metalloproteinases 2 and 3. Finally, we developed an activity assay using an artificial peptide substrate based on the interglobular domain cleavage site (E373-A) of rat aggrecan.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 2002


  • Aggrecan
  • Extracellular matrix
  • Metalloproteinase
  • Proteoglycan

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitorsq'. Together they form a unique fingerprint.

Cite this