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. Windsor, Hernan Grenett, Bente Birkedal-Hansen, M. Kirby Bodden, Jeffrey A. Engler, Henning Birkedal-Hansen

Research output: Contribution to journalArticle

69 Citations (Scopus)

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-á 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-I. This procedure led to the recovery of a single Mr 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 (Mr 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 Mr ≈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 - Aug 15 1993
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 10
Keratinocytes
Genes
Cytokines
Fibroblasts
Chemical activation
Fibroblast Growth Factor 7
Enzyme Precursors
Tissue Inhibitor of Metalloproteinase-1
Protein Sequence Analysis
Transforming Growth Factors
Tetradecanoylphorbol Acetate
Protein Sorting Signals
Caseins
Chromatography
1,2-dihydroxy-4-(nitroethenyl)benzene
Matrix Metalloproteinases
Interleukin-1
Sulfhydryl Compounds
Epidermal Growth Factor

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Windsor, L.; Grenett, Hernan; Birkedal-Hansen, Bente; Bodden, M. Kirby; Engler, Jeffrey A.; Birkedal-Hansen, Henning.

In: Journal of Biological Chemistry, Vol. 268, No. 23, 15.08.1993, p. 17341-17347.

Research output: Contribution to journalArticle

Windsor, L. ; Grenett, Hernan ; Birkedal-Hansen, Bente ; Bodden, M. Kirby ; Engler, Jeffrey A. ; Birkedal-Hansen, Henning. / 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. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 23. pp. 17341-17347.
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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-{\'a} 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-I. This procedure led to the recovery of a single Mr 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 (Mr 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 Mr ≈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.",
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