Publications by authors named "Phillip Ian Bird"

Granzyme K (GzmK) is a tryptic member of the granzyme family of chymotrypsin-like serine proteases produced by cells of the immune system. Previous studies have indicated that GzmK activates protease-activated receptor 1 (PAR1) enhancing activation of monocytes and wound healing in endothelial cells. Here, we show using peptides and full length proteins that GzmK and, to a lesser extent the related protease GzmA, are capable of activating PAR1 and PAR2.

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Article Synopsis
  • * The study highlights that protease inhibitors Serpinb1a and Serpinb6a help keep monocytes and neutrophils alive during both normal and inflammatory conditions by inhibiting an enzyme called cathepsin G (CatG).
  • * It was found that while CatG can activate gasdermin D (GSDMD) to trigger a type of cell death called pyroptosis, deleting GSDMD did not prevent neutrophil death in mice lacking the protease inhibitors, indicating that these inhibitors are crucial for regulating inflammation and cell
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GASPIDs (granule associated serine protease of immune defence) are a family of serine proteases intimately involved with the function of the vertebrate immune system. With the availability of a large and growing set of assembled genomes, we undertook an evolutionary analysis to plot the development of this protein family from a single precursor to the modern mammalian cohort of 12 genes, in an attempt to define and systematically classify subgroups or clades within this family, which are implied by the conventional gene designations. We identified a primordial GASPID gene as either GzmA or GzmK in cartilaginous fish and reconstructed an evolutionary path through to humans.

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Article Synopsis
  • Granzyme B (GrB) is an important enzyme in the immune response, released by cytotoxic lymphocytes to trigger cell death in harmful cells, like cancer or virus-infected ones.
  • * Measuring GrB activity helps scientists understand lymphocyte function, but there are challenges due to differences in how human and mouse GrB reacts to substrates.
  • * This study introduces methods to detect active GrB in human and mouse cells and finds that mouse cells produce significantly more GrB, allowing researchers to use a specific substrate to monitor mouse GrB activity effectively.
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