ArticleThe Journal of cell biology2006
The major human and mouse granzymes are structurally and functionally divergent.
Article in The Journal of cell biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
88 citing papers in PubMed, 195 citations in OpenAlex.
- Differential perforin sensitivity drives lineage-dependent resistance to CAR T-cell killing in blood cancer cell lines.Blood advances · 2026Article
- Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis.The Journal of investigative dermatology · 2025Article
- Natural killer cell-derived granzyme B as a therapeutic target for alleviating graft injury during liver transplantation.Acta pharmaceutica Sinica. B · 2025Article
- Distinct cell death pathways induced by granzymes collectively protect against intestinal Salmonella infection.Mucosal immunology · 2024Article
- Granzyme serine proteases in inflammation and rheumatic diseases.Nature reviews. Rheumatology · 2024Review
- Homodimeric Granzyme A Opsonizes Mycobacterium tuberculosis and Inhibits Its Intracellular Growth in Human Monocytes via Toll-Like Receptor 4 and CD14.The Journal of infectious diseases · 2024Article
- Role of pyroptosis in the pathogenesis of various neurological diseases.Brain, behavior, and immunity · 2024Review
- Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition.Cell death & disease · 2024Article
- In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.Oncoimmunology · 2024Review
- The biological function of Serpinb9 and Serpinb9-based therapy.Frontiers in immunology · 2024Review
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
- Quantifying requirements for mitochondrial apoptosis in CAR T killing of cancer cells.Cell death & disease · 2023Article
- Evolution and immunopathology of chikungunya virus informs therapeutic development.Disease models & mechanisms · 2023Review
- Muscle fiber necroptosis in pathophysiology of idiopathic inflammatory myopathies and its potential as target of novel treatment strategy.Frontiers in immunology · 2023Review
- Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity.Journal of medicinal chemistry · 2022Review
- Urinary detection of early responses to checkpoint blockade and of resistance to it via protease-cleaved antibody-conjugated sensors.Nature biomedical engineering · 2022Article
- Targeting Cancer Cell Ferroptosis to Reverse Immune Checkpoint Inhibitor Therapy Resistance.Frontiers in cell and developmental biology · 2022Review
- Cytolytic CD4Frontiers in immunology · 2022Review
- Granzyme K initiates IL-6 and IL-8 release from epithelial cells by activating protease-activated receptor 2.PloS one · 2022Article
- All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity.Frontiers in immunology · 2022Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 2% of mammalian genes encode proteases. Comparative genomics reveals that those involved in immunity and reproduction show the most interspecies diversity and evidence of positive selection during evolution. This is particularly true of granzymes, the cytotoxic proteases of natural killer cells and CD8+ T cells. There are 5 granzyme genes in humans and 10 in mice, and it is suggested that granzymes evolve to meet species-specific immune challenge through gene duplication and more subtle alterations to substrate specificity. We show that mouse and human granzyme B have distinct structural and functional characteristics. Specifically, mouse granzyme B is 30 times less cytotoxic than human granzyme B and does not require Bid for killing but regains cytotoxicity on engineering of its active site cleft. We also show that mouse granzyme A is considerably more cytotoxic than human granzyme A. These results demonstrate that even "orthologous" granzymes have species-specific functions, having evolved in distinct environments that pose different challenges.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.