ArticleProceedings of the National Academy of Sciences of the United States of America2009
Intact signal peptide of CD18, the beta-subunit of beta2-integrins, renders ruminants susceptible to Mannheimia haemolytica leukotoxin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. 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, 39 citations in OpenAlex.
- Membrane RRM2-positive cells represent a malignant population with cancer stem cell features in intrahepatic cholangiocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Structural basis for non-canonical integrin engagement by Bordetella adenylate cyclase toxin.Cell reports · 2022Article
- Enhancing Animal Disease Resistance, Production Efficiency, and Welfare through Precise Genome Editing.International journal of molecular sciences · 2022Review
- Review
- Extraintestinal PathogenicPathogens (Basel, Switzerland) · 2021Review
- Activation of the PDGF β Receptor by a Persistent Artificial Signal Peptide.Journal of molecular biology · 2021Article
- Review
- Leukotoxin ofToxins · 2018Article
- A bovine CD18 signal peptide variant with increased binding activity toF1000Research · 2018Article
- JMJD8 is a novel endoplasmic reticulum protein with a JmjC domain.Scientific reports · 2017Article
- Precise gene editing paves the way for derivation of Mannheimia haemolytica leukotoxin-resistant cattle.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Uropathogenic Escherichia coli-Associated Exotoxins.Microbiology spectrum · 2016Review
- Interaction of Bacterial Exotoxins with Neutrophil Extracellular Traps: Impact for the Infected Host.Frontiers in microbiology · 2016Review
- Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep.Infection and immunity · 2015Article
- Complete Closed Genome Sequences of a Mannheimia haemolytica Serotype A1 Leukotoxin Deletion Mutant and Its Wild-Type Parent Strain.Genome announcements · 2015Article
- An uncleaved signal peptide directs the Malus xiaojinensis iron transporter protein Mx IRT1 into the ER for the PM secretory pathway.International journal of molecular sciences · 2014Article
- A retained secretory signal peptide mediates high density lipoprotein (HDL) assembly and function of haptoglobin-related protein.The Journal of biological chemistry · 2014Article
- Mannheimia haemolytica and its leukotoxin cause macrophage extracellular trap formation by bovine macrophages.Infection and immunity · 2012Article
- Comparative studies of vertebrate Beta integrin genes and proteins: ancient genes in vertebrate evolution.Biomolecules · 2011Article
- RTX proteins: a highly diverse family secreted by a common mechanism.FEMS microbiology reviews · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal peptides of membrane proteins are cleaved by endoplasmic reticulum-resident signal peptidase, and thus, are not present on mature membrane proteins. Here, we report that, contrary to the paradigm, the signal peptide of ruminant CD18, the beta-subunit of beta(2)-integrins, is not cleaved. Intriguingly, the intact signal peptide of CD18 is responsible for the susceptibility of ruminant leukocytes to Mannheimia (Pasteurella) haemolytica leukotoxin (Lkt). Inhibition of Lkt-induced cytolysis of ruminant leukocytes by CD18 peptide analogs revealed that the Lkt-binding site is formed by amino acids 5-17 of CD18, which, surprisingly, comprise most of the signal sequence. Flow cytometric analysis of ruminant leukocytes indicated the presence of the signal peptide on mature CD18 molecules expressed on the cell surface. Analysis of transfectants expressing CD18 containing the FLAG epitope at the putative cleavage site confirmed that the signal peptide of bovine CD18 is not cleaved. Analysis of the signal sequence of CD18 of eight ruminants and five nonruminants revealed that the signal sequence of CD18 of ruminants contains "cleavage-inhibiting" Q, whereas that of nonruminants contains "cleavage-conducive" G at position -5 relative to the cleavage site. Site-directed mutagenesis of Q to G at position -5 of the signal peptide of bovine CD18 resulted in the cleavage of the signal peptide and abrogation of cytolysis of transfectants expressing bovine CD18 carrying the Q(-5)G mutation. We propose that engineering cattle and other ruminants to contain this mutation would provide a novel technology to render them less susceptible to pneumonic pasteurellosis and concomitant economic losses.
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.