{"id":"348dcef5-2ccc-56d4-9bae-e7443b25fffe","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-wnk4-activates-spak","predicate":"phosphorylates-and-activates","statement":"Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"11dbcc9c-b60d-51aa-a362-bd38f31c0be5","mechanism_event_label":"WNK4 passes a phosphate signal to SPAK.","subject":{"id":"60a8da52-44b6-5714-ae92-2776e6ed5aeb","slug":"wnk4","display_name":"WNK lysine deficient protein kinase 4","entity_type_key":"protein"},"object":{"id":"6ac31e68-8970-5167-aca8-4ce8d90a66cc","slug":"stk39","display_name":"STE20/SPS1-related proline/alanine-rich kinase","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"11dbcc9c-b60d-51aa-a362-bd38f31c0be5","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-wnk4-activates-spak-event","event_type":"biochemical_relationship","label":"WNK4 passes a phosphate signal to SPAK.","description":"Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"60a8da52-44b6-5714-ae92-2776e6ed5aeb","slug":"wnk4","display_name":"WNK lysine deficient protein kinase 4","entity_type_key":"protein"},"role":"causal-subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6ac31e68-8970-5167-aca8-4ce8d90a66cc","slug":"stk39","display_name":"STE20/SPS1-related proline/alanine-rich kinase","entity_type_key":"protein"},"role":"measured-target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"phosphate-donor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"479d0d26-c4f7-596c-bb1b-ebc5163d6f9f","slug":"oxsr1","display_name":"Oxidative stress responsive kinase 1","entity_type_key":"protein"},"role":"parallel-substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"This kinase relay can regulate sodium/chloride transport downstream of K sensing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Primary abstract; kinase-activity and substrate-phosphorylation experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant kinase assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Establishes biochemical capability; not dietary potassium regulation by itself.","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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"WNK4 passes a phosphate signal to SPAK.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[vitari-2005-wnk-spak-osr1] The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases (2005). https://pubmed.ncbi.nlm.nih.gov/16083423/ DOI: 10.1042/BJ20051180","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free assay","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0a60f1df-c46c-5377-a6d5-00553af78d5c","evidence_kind":"source_excerpt","locator":"Lines 151-162","start_line":151,"end_line":162,"excerpt":"### renal-wnk4-activates-spak\nCatalytically active WNK4 phosphorylated and activated SPAK in biochemical assays.\nCondition category: normal\nnutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: WNK4 passes a phosphate signal to SPAK.\norganism: Recombinant proteins\ntissue_or_cell_type: Cell-free assay\nexperimental_model: Recombinant kinase assay\nlimitations: Establishes biochemical capability; not dietary potassium regulation by itself.\ncross_nutrient: This kinase relay can regulate sodium/chloride transport downstream of K sensing.\nevidence_location: Primary abstract; kinase-activity and substrate-phosphorylation experiments.\n[vitari-2005-wnk-spak-osr1] The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases (2005). https://pubmed.ncbi.nlm.nih.gov/16083423/ DOI: 10.1042/BJ20051180","model_system":"Recombinant kinase assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [vitari-2005-wnk-spak-osr1] The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases (2005). https://pubmed.ncbi.nlm.nih.gov/16083423/ DOI: 10.1042/BJ20051180","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}