Cell type-specific regulation of SL-1 and SL-2 genes. Induction of the SL- 2 gene but not the SL-1 gene by human keratinocytes in response to cytokines and phorbolesters

L. J. Windsor, H. Grenett, B. Birkedal-Hansen, M. K. Bodden, J. A. Engler, H. Birkedal-Hansen

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The stromelysin-2 (SL-2) gene is transcriptionally active in normal human keratinocytes and encodes a secreted, catalytically competent but latent matrix metalloproteinase. Phorbolester induction resulted in the emergence of SL-2 (but not SL-1 transcripts), whereas the opposite was true for human mucosal fibroblasts. Expression of keratinocyte SL-2 was also induced by the two keratinocyte growth factors, transforming growth factor-α and epidermal growth factor, by the proinflammatory cytokine, tumor necrosis factor-α, but, somewhat surprisingly, not by interleukin-1β. The latent SL-2 proenzyme was isolated from 12-O-tetradecanoylphorbol-13-acetate-induced keratinocytes by immunoaffinity chromatography using a cross-reactive antibody raised against human SL-1. This procedure led to the recovery of a single M(r) 54,000 molecular species at a level of ≃0.2 μg/ml of culture medium. Amino- terminal sequencing identified the protein as SL-2 and verified the predicted signal sequence cleavage site. Conformational activation of latent SL-2 precursor by SDS gave rise to a full-length, uncleaved (M(r) 54,000) active form and at the same time exposed a cryptic thiol group. By contrast, organomercurial activation resulted in autolytic truncation of the molecule with loss of M(r) ≃10,000 propeptide. SL-2 shared with (human fibroblast) SL-1 the ability to cleave casein, to 'superactivate' fibroblast type procollagenase, and to form apparently binary, SDS-resistant complexes with tissue inhibitor of metalloproteinases-1.

Original languageEnglish (US)
Pages (from-to)17341-17347
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number23
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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