{"id":"e54fedf7-2e03-5c80-9757-45eca8e8d250","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-pka-cftr","predicate":"phosphorylates","statement":"PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2c16d647-7c4f-5365-a5e0-faf8594c9b0a","mechanism_event_label":"A kinase switches the channel into a state that can respond to stimulation.","subject":{"id":"6cd7f461-9b79-5f75-877f-99910bb84f6c","slug":"pka","display_name":"Protein kinase A","entity_type_key":"protein_family"},"object":{"id":"53064670-c3d1-59e8-aeaa-a8d673d00f3a","slug":"cftr","display_name":"Human cystic fibrosis transmembrane conductance regulator / CFTR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2c16d647-7c4f-5365-a5e0-faf8594c9b0a","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-pka-cftr-event","event_type":"biochemical_relationship","label":"A kinase switches the channel into a state that can respond to stimulation.","description":"PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6f35aa38-f875-5759-b749-97a2f6480ff3","slug":"chloride-ion","display_name":"Chloride ion","entity_type_key":"ion"},"role":"conducted_anion","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6cd7f461-9b79-5f75-877f-99910bb84f6c","slug":"pka","display_name":"Protein kinase A","entity_type_key":"protein_family"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"53064670-c3d1-59e8-aeaa-a8d673d00f3a","slug":"cftr","display_name":"Human cystic fibrosis transmembrane conductance regulator / CFTR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/chloride-research/1716180.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5\", \"start_char\": 0, \"end_char\": 961, \"text_sha256\": \"8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"PKA phosphorylation and CFTR mutagenesis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Serines 660, 737, 795 and 813","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Chloride research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"chloride","display_name":"Chloride","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human CFTR in cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A kinase switches the channel into a state that can respond to stimulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CFTR regulatory domain","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4a191119-1284-574d-84b3-1792a425753f","evidence_kind":"source_excerpt","locator":"Lines 237-248","start_line":237,"end_line":248,"excerpt":"### chloride-pka-cftr\nPKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.\nCondition category: normal\nnutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A kinase switches the channel into a state that can respond to stimulation.\norganism: Human CFTR in cells\ntissue_or_cell_type: CFTR regulatory domain\nexperimental_model: PKA phosphorylation and CFTR mutagenesis\nlimitations: Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model.\nexposure: Serines 660, 737, 795 and 813\nevidence_span: {\"source_cache\": \"artifacts/chloride-research/1716180.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5\", \"start_char\": 0, \"end_char\": 961, \"text_sha256\": \"8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5\"}\n[chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. 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