Closed pgaudet closed 11 months ago
The S1 subunit of pertussis toxin from Bordetella pertussis (P04977) "stimulates heterotrimeric GTPase in another organism" Or one could say that it qualifies for "symbiont-mediated activation of host heterotrimeric GTPase". But note that the effect of these depends on whether the host component is suppressive or activating itself. The A subunit (S1) is an ADP-ribosyltransferase that targets host heterotrimeric Gi and Go proteins, preventing signaling from G protein coupled receptors (GPCRs) that activate these proteins. Since these proteins typically inhibit signaling from activated Gs subunits, this results in a potentiation of stimulatory G protein signaling and thus a prolongation of elevated cAMP levels in the cell [PMID:17562776]. Pertussis toxin activity is associated with an extensive upregulation of inflammatory genes at the peak of infection. It also increases the extent and duration of inflammatory responses and pathology in lungs of B. pertussis-infected mice [PMID:23027529]. ->> GO:0075120 symbiont-mediated suppression of host G protein-coupled receptor signal transduction
Culture filitrate protein of 10 kDa (CFP10; EsxB) from Mycobacterium tuberculosis (P9WNK4; P9WNK5) activates host neutrophils, stimulating a transient release of calcium ion which is accompanied by neutrophil chemotaxis and production of reactive oxygen species (ROS). This occurs through an as-yet-unidentified but specific heterotrimeric GPCR. At very high concentrations, CFP-10 is able to permeabilize neutrophils [PMID:25332123]. ->> activating
Cholera toxin subunit CtxA from Vibrio cholerae (P01555; Q6U8A3): Once in the cytosol, the catalytic subunit ADP-ribosylates the heterotrimeric G protein, Gs-alpha, constitutively activating it. This, in turn, activates adenylate cyclase. In the lower gastrointestinal tract, higher levels of cAMP produce an imbalance in electrolyte movement in the epithelial cell--a decrease in sodium ion uptake and an increase in chloride ion expulsion. The net result is abundant fluid loss from the intestine and watery diarrhea. The process can dehydrate the person and cause circulatory system collapse if not rectified [PMID:15963708]. ->> activating
Heat-labile enterotoxin, subunit A (EltA) from Escherichia coli (P06717): The A subunit of the heat-labile enterotoxin is an ADP-ribosyltransferase that covalently modifies the alpha subunit of the Gs GTP-binding protein, resulting in constitutive activation of adenylate cyclase and production of 3′,5′-cyclic AMP (cAMP). Intracellular increases in cAMP lead to activation of the cAMP-dependent protein kinase A (PKA), which phosphorylates the R domain of the cystic fibrosis transmembrane conductance regulator. The resulting chloride and water efflux into the intestinal lumen leads to significant volumes of watery diarrhea [PMID:18978047].
->> activating
Created a new term to capture 'activation':
+[Term] +id: GO:0141104 +name: symbiont-mediated activation of host G protein-coupled receptor signal transduction +namespace: biological_process +def: "A process in which a symbiont G protein-coupled receptor signal transduction pathway in the host organism by initiating, promoting, or enhancing its activation. The host is defined as the larger of the organisms involved in a symbiotic interaction." [PMID:15963708, PMID:18978047, PMID:25332123] +is_a: GO:0075118 ! perturbation of host G protein-coupled receptor signal transduction pathway +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/26164" xsd:anyURI +created_by: pg +creation_date: 2023-09-27T14:13:43Z
@genegodbold Do you have references for these? Do we need a term to describe symbiont-mediated activation of host G protein-coupled receptor signal transduction >> has no references and no annotations?
Might correspond to PATHGO:0000279 | stimulates heterotrimeric GTPase activity in another organism?