{"id":"5414a566-8e73-5d2e-8403-67130860fe93","stable_key":"fd37d270-3395-56d6-9f1c-ddda56e606f6:arg-lysosome-growth","predicate":"required_for","statement":"Leucine generated by lysosomal proteolysis required SLC38A9 for export and subsequent mTORC1 activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d0fa13cb-ad86-5271-8c9e-cc8d21e43169","mechanism_event_label":"Stored or ingested protein must be released from the lysosome before its amino acids can signal.","subject":{"id":"571e470b-c75e-5ef0-aadd-975a1d9d9da5","slug":"slc38a9","display_name":"Human lysosomal amino acid transporter SLC38A9","entity_type_key":"protein"},"object":{"id":"ba496f7a-6955-5256-a13f-cc9251432301","slug":"lysosomal-protein-derived-mtorc1-activation","display_name":"mTORC1 activation from lysosomally degraded protein","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d0fa13cb-ad86-5271-8c9e-cc8d21e43169","stable_key":"fd37d270-3395-56d6-9f1c-ddda56e606f6:arg-lysosome-growth-event","event_type":"observed_relationship","label":"Stored or ingested protein must be released from the lysosome before its amino acids can signal.","description":"Leucine generated by lysosomal proteolysis required SLC38A9 for export and subsequent mTORC1 activation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"571e470b-c75e-5ef0-aadd-975a1d9d9da5","slug":"slc38a9","display_name":"Human lysosomal amino acid transporter SLC38A9","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ba496f7a-6955-5256-a13f-cc9251432301","slug":"lysosomal-protein-derived-mtorc1-activation","display_name":"mTORC1 activation from lysosomally degraded protein","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"eeca3c9e-7749-5677-b7bd-37fe8f7c228d","slug":"arginine","display_name":"L-Arginine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f707c753-cc8c-5f06-90be-bb3d73c60a18","slug":"leucine","display_name":"L-Leucine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cellular proteolysis and mTORC1 experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not evidence that a high blood arginine level guarantees lysosomal amino-acid release.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Arginine collection; tissue, species, dose and formulation distinctions retained.","comparator":null,"unit":null,"notes":"","entity":{"slug":"arginine","display_name":"L-Arginine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Stored or ingested protein must be released from the lysosome before its amino acids can signal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29053970/ · DOI 10.1016/j.cell.2017.09.046","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"cef02f09-36eb-5d7a-8bd2-3fe541fe1d09","evidence_kind":"source_excerpt","locator":"Lines 214-220","start_line":214,"end_line":220,"excerpt":"## arg-lysosome-growth\nStored or ingested protein must be released from the lysosome before its amino acids can signal.\nLeucine generated by lysosomal proteolysis required SLC38A9 for export and subsequent mTORC1 activation.\nModel: Cellular proteolysis and mTORC1 experiments.\nLimitations: Not evidence that a high blood arginine level guarantees lysosomal amino-acid release.\nEvidence access: Primary abstract\nmTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29053970/ · DOI 10.1016/j.cell.2017.09.046","model_system":"Cellular proteolysis and mTORC1 experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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