Characterization of rat uterine matrilysin and its cDNA: Relationship to human pump-1 and activation of procollagenases

Susan R. Abramson, Gregory E Conner, Hideaki Nagase, Isaac Neuhaus, J. Frederick Woessner

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Abstract

A small uterine metalloproteinase of the rat has been shown by amino acid and cDNA sequencing to be orthologous to human pump-1. Both proteinases are now designated as matrilysin or matrix metalloproteinase 7. The properties of purified uterine metalloproteinase and recombinant pump-1 were compared. Their specificities on substrates (gelatins, fibronectin, transferrin, elastin, Azocoll, and (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3,[2, 4-dinitrophenyl]-L-2, 3-diaminopropionyl)-Ala-Arg-NH2) are similar and distinct from those of the stromelysins and gelatinases. The two matrilysins have similar sensitivity to hydroxamate and pseudopeptide inhibitors. Rat matrilysin selectively cleaves the α2(I) chain of rat gelatin, producing major cuts at Gly713-↓-Ile714, Gly775- ↓-Leu776, and Gly809-↓-Ile810. Rat matrilysin produces maximum activation of latent human interstitial collagenase 1 (pro-matrix metalloproteinase 1) when added in the presence of 4-aminophenylmercuric acetate (APMA) by cleaving the Gln80-↓-Phe81 bond. Rat and human matrilysin do not directly activate latent rat collagenase 3 (matrix metalloproteinase 13) and do not enhance its activation when added together with APMA. Autoactivation of collagenase 3 in the presence of APMA results in cleavage at Val81-↓-Tyr82 corresponding to the Gln80-↓-Phe81 cleavage in collagenase 1. Thus collagenase 3 is capable of maximal autoactivation, whereas collagenase 1 is dependent upon another matrix metalloproteinase in order to be activated to its full potential.

Original languageEnglish
Pages (from-to)16016-16022
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number27
StatePublished - Jul 7 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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