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Human Transforming Growth Factor-β Activates a Receptor Serine/Threonine Kinase from the Intravascular ParasiteSchistosoma mansoni
Open accessAbstract
The biology of the helminth parasite Schistosoma mansoni is closely integrated with that of its mammalian host. SmRK1, a divergent type I transforming growth factor-beta (TGF-beta) receptor of unknown ligand specificity, was previously identified as a candidate for a receptor that allows schistosomes to respond to host-derived growth factors. The TGF-beta family includes activin, bone morphogenetic proteins (BMPs), and TGF-beta, all of which can play crucial roles in metazoan development. The downstream signaling protein of receptors that respond to TGF-beta and activin is Smad2, whereas the receptors that respond to BMPs signal via Smad1. When a constitutively active mutant of SmRK1 was overexpressed with either schistosome Smad1 (SmSmad1) or SmSmad2, a receptor-dependent modulation of SmSmad phosphorylation and luciferase reporter activity occurred only with SmSmad2. To evaluate potential ligand activators of SmRK1, a chimeric receptor containing the extracellular domain of SmRK1 joined to the intracellular domain of the human type I TGF-beta receptor was used. The chimeric receptor bound radiolabeled TGF-beta and could activate a luciferase reporter gene in response to both TGF-beta 1 and TGF-beta 3 but not BMP7. Confirmatory results were obtained using full-length SmRK1. These experiments implicate TGF-beta as a ligand for SmRK1 and as a potential host-derived regulator of parasite growth and development.
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Metadata
- Authors
- Beall, M. J., & Pearce, E. J.
- Affiliations
- Cornell University (US)
- Corresponding author
- Pearce, Edward J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 276
- Issue
- 34
- Pages
- 31613-31619
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2023814550
- Cited by
- 67
- References
- 34
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r03ai030985-01)
- National Institute of Allergy and Infectious Diseases (AI30985, F32-AI10513, F32AI010513)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- Schistosoma mansoni, TGF-beta type I receptor, TGF-beta, Smad2, Smad1, host-parasite interactions, chimeric receptors
- MeSH terms
- Amino Acid Sequence, Animals, Enzyme Activation, Humans, Ligands, Mutation, Precipitin Tests, Protein Binding, Schistosoma mansoni, Signal Transduction, Transforming Growth Factor beta, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Receptors, Transforming Growth Factor beta
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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