The role of intracellular proteinases in human neutrophil activation.
In addition to other proteinases human neutrophils contain two non granular neutral endopeptidases: a serine proteinase and a cysteine Ca2+ dependent proteinase named calpain. Serine proteinase localized in association with the cytoskeleton-membrane proteins, apparently exerts a dual role: it is partially released into the medium during neutrophil stimulation by phorbol myristate acetate (PMA), presumably acting as one of the cytotoxic factors; and in its intracellular localization is presumably involved in the process of down regulation of native protein kinase C (PKC). Calpain, predominantly present in resting conditions in an inactive form, becomes activated in the course of neutrophil stimulation and appears to be involved both in the down regulation of native PKC as well as in the formation of a proteinase-activated kinase form, presumably derived from PKC and defined as PKC-M. Calpain once activated appears to be also involved in cytoskeleton rearrangement, through proteolytic degradation specifically oriented by substrate phosphorylation. Activation, down regulation of PKC, formation of the proteinase-activated kinase, as well as proteolytic processing of cytoskeleton have been demonstrated to be correlated to those biochemical responses which characterize neutrophil activation.
Pontremoli
S
S
Institute of Biological Chemistry, University of Genoa, Italy.
Melloni
E
E
D002154:Calpain / Q000502:physiology*; D002451:Cell Compartmentation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000201:enzymology; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012697:Serine Endopeptidases / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D010750:Phosphoproteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D012697:Serine Endopeptidases; D002154:Calpain; D013755:Tetradecanoylphorbol Acetate