Molecular cloning, chromosomal localization, and bacterial expression of a murine macrophage metalloelastase

S. D. Shapiro, G. L. Griffin, D. J. Gilbert, N. A. Jenkins, N. G. Copeland, H. G. Welgus, R. M. Senior, T. J. Ley

Research output: Contribution to journalArticlepeer-review

176 Scopus citations


Murine macrophages have previously been shown to secrete a zinc-dependent proteinase that can degrade elastin. In this report, we identify murine macrophage elastase (MME) cDNA and show that it is a distinct member of the metalloproteinase gene family. Small amounts of MME were purified to homogeneity, and N-terminal amino acid sequence was obtained. This sequence was used to obtain a partial cDNA clone by the poly merase chain reaction; a cDNA library derived from a mouse macrophage-like cell line (P388D1) was screened with this probe. A full-length MME cDNA spanning ∼1.8 kilobases contained an open reading frame of 1386 base pairs; the predicted molecular mass of the MME proenzyme is 53 kDa. The gene encoding MME is represented only once in the mouse genome and is located on chromosome 9. Despite a size that is similar to other metalloproteinases, MME is distinct, sharing only 33-48% amino acid homology with other metalloproteinases. In contrast to other metalloenzymes, MME appears to be rapidly processed to an active truncated form (N-terminal and C-terminal cleavage). We expressed recombinant MME in Escherichia coli and demonstrated that it has significant elastolytic activity that is specifically inhibited by the tissue inhibitor of metalloproteinases. MME is therefore a true metalloproteinase that may be involved in tissue injury and remodeling.

Original languageEnglish (US)
Pages (from-to)4664-4671
Number of pages8
JournalJournal of Biological Chemistry
Issue number7
StatePublished - 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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