{"id":"0c7bb319-69bf-53cd-9e2c-4e7f503d943b","stable_key":"1ff3a29f-ef80-5bff-9300-30b98c60b90d:strontium-thyroid-bias","predicate":"biases_signaling","statement":"In rat medullary thyroid carcinoma 6-23 cells, strontium biased CaSR signaling toward ERK1/2 relative to Gq/11 and intracellular-calcium mobilization compared with calcium.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d9ca3200-6fdd-508d-a195-c179f1633b7d","mechanism_event_label":"The same receptor can send different relative signals depending on the ion.","subject":{"id":"97607549-3a37-544e-b6e6-266887f7c35f","slug":"strontium-ion","display_name":"Strontium ion / Sr2+","entity_type_key":"ion"},"object":{"id":"67c9319b-f42a-5b79-807f-8009a5401245","slug":"rat-casr","display_name":"Rat calcium-sensing receptor / Casr","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"d9ca3200-6fdd-508d-a195-c179f1633b7d","stable_key":"1ff3a29f-ef80-5bff-9300-30b98c60b90d:strontium-thyroid-bias-event","event_type":"observed_relationship","label":"The same receptor can send different relative signals depending on the ion.","description":"In rat medullary thyroid carcinoma 6-23 cells, strontium biased CaSR signaling toward ERK1/2 relative to Gq/11 and intracellular-calcium mobilization compared with calcium.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"97607549-3a37-544e-b6e6-266887f7c35f","slug":"strontium-ion","display_name":"Strontium ion / Sr2+","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"67c9319b-f42a-5b79-807f-8009a5401245","slug":"rat-casr","display_name":"Rat calcium-sensing receptor / Casr","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2ca2864b-1ef0-54e4-8397-1dbe7207a0d2","slug":"strontium","display_name":"Strontium","entity_type_key":"nutrient_element"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat C-cell model; concentration-response measurements across six signaling outputs.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biased agonism is model- and assay-dependent; not a direct human thyroid-hormone effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"strontium","display_name":"Strontium","entity_type_key":"nutrient_element"}},{"dimension":"plain_language","value_text":"The same receptor can send different relative signals depending on the ion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22942242/ · DOI 10.1124/jpet.112.197210","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4be60a46-106f-5b4e-97fe-2a1fec2d5597","evidence_kind":"source_excerpt","locator":"Lines 342-348","start_line":342,"end_line":348,"excerpt":"## strontium-thyroid-bias\nThe same receptor can send different relative signals depending on the ion.\nIn rat medullary thyroid carcinoma 6-23 cells, strontium biased CaSR signaling toward ERK1/2 relative to Gq/11 and intracellular-calcium mobilization compared with calcium.\nModel: Rat C-cell model; concentration-response measurements across six signaling outputs.\nLimitations: Biased agonism is model- and assay-dependent; not a direct human thyroid-hormone effect.\nEvidence access: Primary abstract\nStrontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22942242/ · DOI 10.1124/jpet.112.197210","model_system":"Rat C-cell model; concentration-response measurements across six signaling outputs.","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":"43ef0fe7-eb6c-5346-8381-f7694733b4dc","stable_key":"import-1ff3a29f-ef80-5bff-9300-30b98c60b90d","title":"Strontium: calcium interactions, cellular mechanisms and mineralization (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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