{"id":"0fe07b61-ff90-56ed-9a1d-657510ddb96f","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-tars2-repletion-failure","predicate":"is_required_for","statement":"Cells lacking TARS2 failed to restore mTORC1 activation in response to threonine repletion; cytosolic TARS was not required for this signaling effect.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5d89bbdc-b8e5-5678-8c36-1837216ddcc0","mechanism_event_label":"Restoring the nutrient did not restore the signal when its machinery was missing.","subject":{"id":"e1304998-8f29-56cc-8535-e65d11c53582","slug":"tars2","display_name":"Human mitochondrial threonyl-tRNA synthetase / TARS2","entity_type_key":"protein"},"object":{"id":"b66a586b-c9c8-5dab-ab40-dd0a395be458","slug":"human-threonine-mtorc1-repletion","display_name":"Threonine-responsive human cellular mTORC1 activation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5d89bbdc-b8e5-5678-8c36-1837216ddcc0","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-tars2-repletion-failure-event","event_type":"observed_relationship","label":"Restoring the nutrient did not restore the signal when its machinery was missing.","description":"Cells lacking TARS2 failed to restore mTORC1 activation in response to threonine repletion; cytosolic TARS was not required for this signaling effect.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e1304998-8f29-56cc-8535-e65d11c53582","slug":"tars2","display_name":"Human mitochondrial threonyl-tRNA synthetase / TARS2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b66a586b-c9c8-5dab-ab40-dd0a395be458","slug":"human-threonine-mtorc1-repletion","display_name":"Threonine-responsive human cellular mTORC1 activation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9f025af3-f039-517f-908b-4af6fc65415e","slug":"mtorc1","display_name":"Mechanistic target of rapamycin complex 1","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"42b7656b-93a3-5348-a7cf-775072512653","slug":"tars1","display_name":"Human cytosolic threonyl-tRNA synthetase / TARS1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"TARS2 loss and threonine repletion in cultured cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is a signaling endpoint, not a clinical threonine-repletion trial.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Restoring the nutrient did not restore the signal when its machinery was missing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"0e5d332f-75ba-5597-a73c-745993371e53","evidence_kind":"source_excerpt","locator":"Lines 106-112","start_line":106,"end_line":112,"excerpt":"## l-threonine-tars2-repletion-failure\nRestoring the nutrient did not restore the signal when its machinery was missing.\nCells lacking TARS2 failed to restore mTORC1 activation in response to threonine repletion; cytosolic TARS was not required for this signaling effect.\nModel: TARS2 loss and threonine repletion in cultured cells.\nLimitations: This is a signaling endpoint, not a clinical threonine-repletion trial.\nEvidence access: Primary abstract\nMitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036","model_system":"TARS2 loss and threonine repletion in cultured cells.","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":"35396730-235a-537e-8a05-c6ef2960c509","stable_key":"import-97957230-601f-5dec-8524-0812be8fadbf","title":"L-Threonine: translation, intestinal barrier, metabolism 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. 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