ArticleJournal of immunology (Baltimore, Md. : 1950)2010
How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity and protection of virulence-associated cell wall proteins.PLoS pathogens · 2013Trial
- Lubricin's Mucin Domain Has Strong Polyproline Type II Helical Character.Computational and structural biotechnology journal · 2026Article
- Species Differences in Platelet Protease-Activated Receptors.International journal of molecular sciences · 2023Review
- Mechanistic underpinning of an inside-out concept for autoimmunity in multiple sclerosis.Annals of clinical and translational neurology · 2021Review
- Article
- Hindrance of the Proteolytic Activity of Neutrophil-Derived Serine Proteases by Serine Protease Inhibitors as a Management of Cardiovascular Diseases and Chronic Inflammation.Frontiers in chemistry · 2021Review
- Activity-Based Probes to Utilize the Proteolytic Activity of Cathepsin G in Biological Samples.Frontiers in chemistry · 2021Review
- Application of an Activity-Based Probe to Determine Proteolytic Activity of Cell Surface Cathepsin G by Mass Cytometry Data Acquisition.ACS omega · 2020Article
- A Tolerogenic Role of Cathepsin G in a Primate Model of Multiple Sclerosis: Abrogation by Epstein-Barr Virus Infection.Archivum immunologiae et therapiae experimentalis · 2020Review
- Potent and Broad but not Unselective Cleavage of Cytokines and Chemokines by Human Neutrophil Elastase and Proteinase 3.International journal of molecular sciences · 2020Article
- Long noncoding RNA expression profile from cryptococcal meningitis patients identifies DPY19L1p1 as a new disease marker.CNS neuroscience & therapeutics · 2019Article
- Extended Cleavage Specificity of Human Neutrophil Elastase, Human Proteinase 3, and Their Distant Ortholog Clawed Frog PR3-Three Elastases With Similar Primary but Different Extended Specificities and Stability.Frontiers in immunology · 2018Article
- Article
- A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model.Frontiers in immunology · 2017Review
- Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Mast cell proteases as pharmacological targets.European journal of pharmacology · 2016Review
- Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux.PloS one · 2015Article
- Following the digestion of milk proteins from mother to baby.Journal of proteome research · 2014Article
- Identification and characterization of circulating variants of CXCL12 from human plasma: effects on chemotaxis and mobilization of hematopoietic stem and progenitor cells.Stem cells and development · 2014Article
- Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors.The Journal of biological chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Cathepsin G is a major secreted serine peptidase of neutrophils and mast cells. Studies in Ctsg-null mice suggest that cathepsin G supports antimicrobial defenses but can injure host tissues. The human enzyme has an unusual "Janus-faced" ability to cleave peptides at basic (tryptic) as well as aromatic (chymotryptic) sites. Tryptic activity has been attributed to acidic Glu(226) in the primary specificity pocket and underlies proposed important functions, such as activation of prourokinase. However, most mammals, including mice, substitute Ala(226) for Glu(226), suggesting that human tryptic activity may be anomalous. To test this hypothesis, human cathepsin G was compared with mouse wild-type and humanized active site mutants, revealing that mouse primary specificity is markedly narrower than that of human cathepsin G, with much greater Tyr activity and selectivity and near absence of tryptic activity. It also differs from human in resisting tryptic peptidase inhibitors (e.g., aprotinin), while favoring angiotensin destruction at Tyr(4) over activation at Phe(8). Ala(226)Glu mutants of mouse cathepsin G acquire tryptic activity and human ability to activate prourokinase. Phylogenetic analysis reveals that the Ala(226)Glu missense mutation appearing in primates 31-43 million years ago represented an apparently unprecedented way to create tryptic activity in a serine peptidase. We propose that tryptic activity is not an attribute of ancestral mammalian cathepsin G, which was primarily chymotryptic, and that primate-selective broadening of specificity opposed the general trend of increased specialization by immune peptidases and allowed acquisition of new functions.
Indexed as
Identifiers
What OpenQuestion holds
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.