Membrane-type matrix metalloproteinase 1 is a gelatinolytic enzyme and is secreted in a complex with tissue inhibitor of metalloproteinases

Kazushi Imai, Eiko Ohuchi, Takanori Aoki, Hidehiro Nomura, Yutaka Fujii, Hiroshi Sato, Motoharu Seiki, Yasunori Okada

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Abstract

The processing mechanism and gelatinolytic activity of the membrane-type matrix metalloproteinase 1 (MT-MMP-1) were examined by expressing in COS-1 cells a deletion mutant of MT-MMP-1 lacking the transmembrane domain (ΔMT1) and its site-directed mutant with a furin-resistant sequence in the propeptide domain (mutant ΔMT1). ΔMT1, but not mutant ΔMT1, was processed to an active form and exhibited gelatinolytic activity as seen using gelatin zymography. ΔMT1 isolated in a complex form with tissue inhibitor of metalloproteinases 2 (TIMP-2) from the stable transfectants demonstrated the NH2-terminal sequence of Ala113-Ile-Gln-Gly-Leu, indicating cleavage at one amino acid down-stream from the furin recognition sequence. The ΔMT1/TIMP-2 complex formed a ternary complex with proMMP-2 through the COOH termini of TIMP-2 and proMMP-2. A human breast carcinoma cell line (MDA-MB-231 cells) also secreted MT-MMP-1 into culture media, which was purified in a complex form with TIMP-2 and showed gelatinolytic activity as seen using zymography. These results demonstrate for the first time that MT-MMP-1 is a gelatinolytic enzyme and secreted from cells in a complex with TIMP-2, which can form a ternary complex of MT-MMP-1/TIMP-2/proMMP-2.

Original languageEnglish
Pages (from-to)2707-2710
Number of pages4
JournalCancer Research
Volume56
Issue number12
Publication statusPublished - 1996 Jun 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Imai, K., Ohuchi, E., Aoki, T., Nomura, H., Fujii, Y., Sato, H., Seiki, M., & Okada, Y. (1996). Membrane-type matrix metalloproteinase 1 is a gelatinolytic enzyme and is secreted in a complex with tissue inhibitor of metalloproteinases. Cancer Research, 56(12), 2707-2710.