{"id":"03ca71a3-d3d1-5d33-a5e1-38b5fab9e314","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-akt","predicate":"activates_tested","statement":"In HEK293 experiments, imidazole propionate increased basal Akt phosphorylation; p38-gamma knockdown blocked the Akt and inhibitory AMPK phosphorylation responses.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e4e54987-000e-5640-a394-2a147a144cf1","mechanism_event_label":"A microbial product changed a kinase pathway, and removing one kinase interrupted the response.","subject":{"id":"06c093ed-025c-54bc-8016-6a3da64ffbf9","slug":"imidazole-propionate","display_name":"Imidazole propionate","entity_type_key":"small_molecule"},"object":{"id":"a13cb592-c939-5f92-9206-d774248802fc","slug":"akt-proteins","display_name":"AKT serine/threonine kinase family","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"e4e54987-000e-5640-a394-2a147a144cf1","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-akt-event","event_type":"observed_relationship","label":"A microbial product changed a kinase pathway, and removing one kinase interrupted the response.","description":"In HEK293 experiments, imidazole propionate increased basal Akt phosphorylation; p38-gamma knockdown blocked the Akt and inhibitory AMPK phosphorylation responses.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"06c093ed-025c-54bc-8016-6a3da64ffbf9","slug":"imidazole-propionate","display_name":"Imidazole propionate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a13cb592-c939-5f92-9206-d774248802fc","slug":"akt-proteins","display_name":"AKT serine/threonine kinase family","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"48fe76e5-ccdd-5eeb-8c82-4fe742c17a03","slug":"mapk12","display_name":"Human p38-gamma MAP kinase / MAPK12","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HEK293 cells; time-dependent signaling, siRNA and recombinant-kinase validation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Basal activation differs from insulin-stimulated activation. Recombinant assay construct species is not inferred from the human host cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A microbial product changed a kinase pathway, and removing one kinase interrupted the response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7e41b715-a29c-5662-b7fe-b8f991533b6f","evidence_kind":"source_excerpt","locator":"Lines 322-328","start_line":322,"end_line":328,"excerpt":"## histidine-imp-akt\nA microbial product changed a kinase pathway, and removing one kinase interrupted the response.\nIn HEK293 experiments, imidazole propionate increased basal Akt phosphorylation; p38-gamma knockdown blocked the Akt and inhibitory AMPK phosphorylation responses.\nModel: Human HEK293 cells; time-dependent signaling, siRNA and recombinant-kinase validation.\nLimitations: Basal activation differs from insulin-stimulated activation. Recombinant assay construct species is not inferred from the human host cells.\nEvidence access: Primary full text\nMicrobial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012","model_system":"Human HEK293 cells; time-dependent signaling, siRNA and recombinant-kinase validation.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"cb672530ec8b4a4542d0f3957e80ca76bb0449e9f988845b0f7681f623c4ec9b","revision_id":"19a7f26c-d9a1-5411-a81d-025f3d98a452","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}