An unusual specificity in the activation of neutrophil serine proteinase zymogens

G Salvesen, J J Enghild

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    85 Citations (Scopus)

    Abstract

    The majority of proteinases exist as zymogens whose activation usually results from a single proteolytic event. Two notable exceptions to this generalization are the serine proteinases neutrophil elastase (HNE) and cathepsin G (cat G), proteolytic enzymes of human neutrophils that are apparently fully active in their storage granules. On the basis of amino acid sequences inferred from the gene and cDNAs encoding these enzymes, it is likely that both are synthesized as precursors containing unusual C-terminal and N-terminal peptide extensions absent from the mature proteins. We have used biosynthetic radiolabeling and radiosequencing techniques to identify the kinetics of activation of both proteinases in the promonocyte-like cell line U937. We find that both N- and C-terminal extensions are removed about 90 min after the onset of synthesis, resulting in the activation of the proteinases. HNE and cat G are, therefore, transiently present as zymogens, presumably to protect the biosynthetic machinery of the cell from adventitious proteolysis. Activation results from cleavage following a glutamic acid residue to give an activation specificity opposite to those of almost all other serine proteinase zymogens, but shared, possibly, by the "granzyme" group of related serine proteinases present in the killer granules of cytotoxic T-lymphocytes and rat mast cell proteinase II.
    Original languageEnglish
    JournalBiochemistry
    Volume29
    Issue22
    Pages (from-to)5304-8
    Number of pages4
    ISSN0006-2960
    Publication statusPublished - 1990

    Keywords

    • Amino Acid Sequence
    • Cathepsins
    • Cell Line
    • Enzyme Activation
    • Enzyme Precursors
    • Isotope Labeling
    • Kinetics
    • Leukocyte Elastase
    • Molecular Sequence Data
    • Neutrophils
    • Pancreatic Elastase
    • Protein Processing, Post-Translational
    • Serine Endopeptidases

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