Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo.
Journal:
Proc. Natl. Acad. Sci. U.S.A. 1999 JulAuthors:
Pham CT, Ley TJ
Abstract
Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been implicated in the processing of granzymes, which are neutral serine proteases exclusively expressed in the granules of activated cytotoxic lymphocytes. In this report, we show that cytotoxic lymphocytes derived from DPPI-/- mice contain normal amounts of granzymes A and B, but these molecules retain their prodipeptide domains and are inactive. Cytotoxic assays with DPPI-/- effector cells reveal severe defects in the ind
...[more]uction of target cell apoptosis (as measured by [(125)I]UdR release) at both early and late time points; this defect is comparable to that detected in perforin-/- or granzyme A-/- x B-/- cytotoxic lymphocytes. DPPI therefore plays an essential role in the in vivo processing and activation of granzymes A and B, which are required for cytotoxic lymphocyte granule-mediated apoptosis.[less]
Mesh Headings:
Animals, Apoptosis, Cathepsin C, Cytoplasmic Granules, Cytotoxicity Tests, Immunologic, Deoxyuridine, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Enzyme Activation, Flow Cytometry, Gene Targeting, Granzymes, Killer Cells, Lymphokine-Activated, Membrane Glycoproteins, Mice, Mice, Knockout, Perforin, Pore Forming Cytotoxic Proteins, Protein Precursors, Serine Endopeptidases, T-Lymphocytes, Cytotoxic