{"id":"0b5c3380-ecf5-5e22-bfd6-672a4f291315","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-pp1a-dephosphorylates-ncc","predicate":"binds-and-dephosphorylates","statement":"PP1A directly bound the NCC regulatory terminus and dephosphorylated NCC; high extracellular K enhanced their association in MDCKI-hNCC cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"1ce0fe82-4336-5cac-94ae-3fd7ba41f8e0","mechanism_event_label":"Potassium can increase contact between NCC and an enzyme that removes its phosphate signal.","subject":{"id":"b55664da-4c75-5475-8448-23d51e5de0ee","slug":"ppp1ca","display_name":"Protein phosphatase 1 catalytic subunit alpha","entity_type_key":"protein"},"object":{"id":"63291643-1df9-5547-952a-9082838a350e","slug":"slc12a3","display_name":"Thiazide-sensitive sodium-chloride cotransporter","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1ce0fe82-4336-5cac-94ae-3fd7ba41f8e0","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-pp1a-dephosphorylates-ncc-event","event_type":"biochemical_relationship","label":"Potassium can increase contact between NCC and an enzyme that removes its phosphate signal.","description":"PP1A directly bound the NCC regulatory terminus and dephosphorylated NCC; high extracellular K enhanced their association in MDCKI-hNCC cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b55664da-4c75-5475-8448-23d51e5de0ee","slug":"ppp1ca","display_name":"Protein phosphatase 1 catalytic subunit alpha","entity_type_key":"protein"},"role":"causal-subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"63291643-1df9-5547-952a-9082838a350e","slug":"slc12a3","display_name":"Thiazide-sensitive sodium-chloride cotransporter","entity_type_key":"protein"},"role":"measured-target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"role":"regulator","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8197e69c-215b-5cd4-bf4b-edde6708ea8f","slug":"ncc-phosphorylation","display_name":"NCC phosphorylation","entity_type_key":"cellular_process"},"role":"readout","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"K-dependent phosphatase engagement reduces the activation signal of the Na/Cl transporter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 6A-C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified binding/phosphatase assays and MDCKI-hNCC cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Binding/activity assays do not by themselves quantify sodium transport in humans.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Potassium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"potassium","display_name":"Potassium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Recombinant proteins; Canis lupus familiaris cell line expressing human NCC","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Potassium can increase contact between NCC and an enzyme that removes its phosphate signal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[grimm-2023-pp1a-ncc] Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure (2023). https://www.jci.org/articles/view/158498 DOI: 10.1172/JCI158498","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free and kidney-derived cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"85996606-05cf-5b78-a050-eb06f713877f","evidence_kind":"source_excerpt","locator":"Lines 268-279","start_line":268,"end_line":279,"excerpt":"### renal-pp1a-dephosphorylates-ncc\nPP1A directly bound the NCC regulatory terminus and dephosphorylated NCC; high extracellular K enhanced their association in MDCKI-hNCC cells.\nCondition category: normal\nnutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Potassium can increase contact between NCC and an enzyme that removes its phosphate signal.\norganism: Recombinant proteins; Canis lupus familiaris cell line expressing human NCC\ntissue_or_cell_type: Cell-free and kidney-derived cells\nexperimental_model: Purified binding/phosphatase assays and MDCKI-hNCC cells\nlimitations: Binding/activity assays do not by themselves quantify sodium transport in humans.\ncross_nutrient: K-dependent phosphatase engagement reduces the activation signal of the Na/Cl transporter.\nevidence_location: Figure 6A-C.\n[grimm-2023-pp1a-ncc] Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure (2023). https://www.jci.org/articles/view/158498 DOI: 10.1172/JCI158498","model_system":"Purified binding/phosphatase assays and MDCKI-hNCC cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [grimm-2023-pp1a-ncc] Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure (2023). https://www.jci.org/articles/view/158498 DOI: 10.1172/JCI158498","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"241226ee-6b7d-5cc7-9781-e6beb8ee1982","stable_key":"import-5102beb6-9f61-500e-af10-9ac63649e0b7","title":"Potassium: cross-nutrient mechanisms and deficiency (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"a8f89f8d84b48c0f93048dfc45f7f57a67dd9a7249968a096a14aeb03d8b7a52","revision_id":"de4ec6f4-58a1-537b-8169-97b783898df1","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}