{"id":"b162c972-8c35-59c9-9514-e73102261b40","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-phospho-nedd4l-releases-enac","predicate":"increases","statement":"SGK-dependent Nedd4-2 phosphorylation reduced its ENaC interaction and increased ENaC surface expression in oocytes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"87b667ea-6d89-5d7a-bebd-b6a0a5d52dcd","mechanism_event_label":"Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface.","subject":{"id":"e3d88ab0-725b-5cd0-9740-dee1509d4a1e","slug":"nedd4l-sgk-phosphorylated","display_name":"SGK-phosphorylated NEDD4L","entity_type_key":"protein_state"},"object":{"id":"1d704305-d296-50a9-88bd-68e3ce08627c","slug":"enac-surface-abundance","display_name":"ENaC surface abundance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"87b667ea-6d89-5d7a-bebd-b6a0a5d52dcd","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-phospho-nedd4l-releases-enac-event","event_type":"biochemical_relationship","label":"Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface.","description":"SGK-dependent Nedd4-2 phosphorylation reduced its ENaC interaction and increased ENaC surface expression in oocytes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e3d88ab0-725b-5cd0-9740-dee1509d4a1e","slug":"nedd4l-sgk-phosphorylated","display_name":"SGK-phosphorylated NEDD4L","entity_type_key":"protein_state"},"role":"causal-subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1d704305-d296-50a9-88bd-68e3ce08627c","slug":"enac-surface-abundance","display_name":"ENaC surface abundance","entity_type_key":"cellular_process"},"role":"measured-target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"11e2d9a3-7d3c-5b2c-938d-5a25b15d10d1","slug":"nedd4l","display_name":"NEDD4-like E3 ubiquitin protein ligase","entity_type_key":"protein"},"role":"unmodified-reference","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b6e8049f-ad5c-5ca0-ba73-1d4392131397","slug":"enac","display_name":"Epithelial sodium channel","entity_type_key":"protein_complex"},"role":"regulated-channel","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"4db8cea5-2f5d-5df0-881a-a725d1920e85","slug":"sgk1","display_name":"Serum and glucocorticoid-regulated kinase 1","entity_type_key":"protein"},"role":"upstream-kinase","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"38de8704-84db-5770-ac1d-242cd787e798","slug":"sodium-ion","display_name":"Sodium ion","entity_type_key":"ion"},"role":"current-carrier","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Higher sodium-channel availability can support the secretory machinery used for K balance.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figures 3-5; interaction and anti-FLAG surface-labeling experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Oocyte binding, current and surface-labeling assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Molecular sufficiency does not establish exclusive control in intact kidneys.","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":"Xenopus laevis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Oocytes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e7c44342-11e8-52fd-a48a-91ea0a599441","evidence_kind":"source_excerpt","locator":"Lines 421-432","start_line":421,"end_line":432,"excerpt":"### renal-phospho-nedd4l-releases-enac\nSGK-dependent Nedd4-2 phosphorylation reduced its ENaC interaction and increased ENaC surface expression in oocytes.\nCondition category: normal\nnutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface.\norganism: Xenopus laevis\ntissue_or_cell_type: Oocytes\nexperimental_model: Oocyte binding, current and surface-labeling assays\nlimitations: Molecular sufficiency does not establish exclusive control in intact kidneys.\ncross_nutrient: Higher sodium-channel availability can support the secretory machinery used for K balance.\nevidence_location: Figures 3-5; interaction and anti-FLAG surface-labeling experiments.\n[debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052","model_system":"Oocyte binding, current and surface-labeling assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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