{"id":"4390f5d8-6385-58a3-acf1-834c86ccc646","stable_key":"507ed066-fd6d-5722-9223-97b66302e7e3:glycine-gpr158-kinase-dependence","predicate":"supports_tested","statement":"Blocking PKA or ERK signaling suppressed the glycine-associated increase in medium-spiny-neuron excitability; ERK and Kv7.2 serine phosphorylation increased in the study.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ae120bca-e2ff-5fde-bd2e-300eacb2c13f","mechanism_event_label":"The channel response depends on intracellular signaling steps.","subject":{"id":"bf2efe34-f901-563d-b496-c7bd482335eb","slug":"mouse-nac-pka-erk-signaling","display_name":"PKA/ERK signaling in mouse accumbens neurons","entity_type_key":"cellular_process"},"object":{"id":"78642f02-4d72-54a1-bb9e-0e6271b1396a","slug":"mouse-nac-glycine-excitability","display_name":"Glycine-sensitive excitability in mouse accumbens neurons","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ae120bca-e2ff-5fde-bd2e-300eacb2c13f","stable_key":"507ed066-fd6d-5722-9223-97b66302e7e3:glycine-gpr158-kinase-dependence-event","event_type":"observed_relationship","label":"The channel response depends on intracellular signaling steps.","description":"Blocking PKA or ERK signaling suppressed the glycine-associated increase in medium-spiny-neuron excitability; ERK and Kv7.2 serine phosphorylation increased in the study.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"bf2efe34-f901-563d-b496-c7bd482335eb","slug":"mouse-nac-pka-erk-signaling","display_name":"PKA/ERK signaling in mouse accumbens neurons","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"78642f02-4d72-54a1-bb9e-0e6271b1396a","slug":"mouse-nac-glycine-excitability","display_name":"Glycine-sensitive excitability in mouse accumbens neurons","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2b507258-430c-51fe-9fd2-e510c2c197a9","slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4c84160f-6db7-5bb4-aef1-a0c964306831","slug":"mouse-gpr158","display_name":"Mouse metabotropic glycine receptor / Gpr158","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"81dbde00-3e93-5687-a194-5d5529412cdf","slug":"mouse-kcnq2","display_name":"Mouse Kv7.2 / Kcnq2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse slice pharmacological inhibition and phosphorylation assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Associated phosphorylation and inhibitor effects do not establish every kinase-substrate step; cholinergic interneurons did not share the firing response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The channel response depends on intracellular signaling steps.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d08a08c2-7631-54ba-b5d9-a57790aa9041","evidence_kind":"source_excerpt","locator":"Lines 266-272","start_line":266,"end_line":272,"excerpt":"## glycine-gpr158-kinase-dependence\nThe channel response depends on intracellular signaling steps.\nBlocking PKA or ERK signaling suppressed the glycine-associated increase in medium-spiny-neuron excitability; ERK and Kv7.2 serine phosphorylation increased in the study.\nModel: Mouse slice pharmacological inhibition and phosphorylation assays.\nLimitations: Associated phosphorylation and inhibitor effects do not establish every kinase-substrate step; cholinergic interneurons did not share the firing response.\nEvidence access: Primary full text\nGlycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w","model_system":"Mouse slice pharmacological inhibition and phosphorylation assays.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"7b2859d8-e2bf-51e7-8e32-0715c10cbc49","stable_key":"import-507ed066-fd6d-5722-9223-97b66302e7e3","title":"Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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