Meprins process matrix metalloproteinase-9 (MMP-9)/gelatinase B and enhance the activation kinetics by MMP-3

FEBS Lett. 2012 Dec 14;586(24):4264-9. doi: 10.1016/j.febslet.2012.10.033. Epub 2012 Nov 1.

Abstract

Meprin α and β, members of the astacin family of zinc metalloproteinases, are unique plasma membrane and secreted proteases known to cleave a wide range of biological substrates involved in inflammation, cancer and fibrosis. In this study, we identified proMMP-9 as a novel substrate and show that aminoterminal meprin-mediated clipping improves the activation kinetics of proMMP-9 by MMP-3, an efficient activator of proMMP-9. Interestingly, the NH(2)-terminus LVLFPGDL, generated by incubation with meprin α, is identical to the form produced in conditioned media from human neutrophils and monocytes. Hence, this meprin-mediated processing and enhancement of MMP-9 activation kinetics may have biological relevance in the context of in vivo inflammatory processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cells, Cultured / metabolism
  • Culture Media, Conditioned
  • Humans
  • Matrix Metalloproteinase 3 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Molecular Sequence Data
  • Monocytes / metabolism
  • Neutrophils / metabolism
  • Tiopronin / metabolism*

Substances

  • Culture Media, Conditioned
  • Tiopronin
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9