{"id":"9a4f0bd4-b245-573f-9fb9-5c1439ab80cb","stable_key":"research:cd45-y505","predicate":"dephosphorylates_to_relieve_inhibition_of","statement":"CD45 removal of inhibitory LCK Y505 phosphorylation can favor an open activation-competent state.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"positive","is_public":true,"mechanism_event_id":"4f18dd46-5270-5489-9fd3-044cb506a490","mechanism_event_label":"Removing the Y505 phosphate can release LCK inhibition.","subject":{"id":"f1d38046-6772-515b-9276-9b38748ae601","slug":"ptprc","display_name":"PTPRC","entity_type_key":"protein"},"object":{"id":"7a4df9a1-d64b-56ca-aada-ed349e74008d","slug":"lck-activation","display_name":"LCK activation competence","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4f18dd46-5270-5489-9fd3-044cb506a490","stable_key":"research:cd45-y505","event_type":"dephosphorylation","label":"Removing the Y505 phosphate can release LCK inhibition.","description":"CD45 removal of inhibitory LCK Y505 phosphorylation can favor an open activation-competent state.","status":"active","compartment":null,"participants":[{"entity":{"id":"77666cb0-1f2b-5b9c-92af-dbbee0866b92","slug":"lck-py505","display_name":"LCK phosphorylated at Y505","entity_type_key":"protein_state"},"role":"substrate","stoichiometry":null,"state_label":"Y505 phosphorylated","sequence_order":0,"notes":""},{"entity":{"id":"50347559-680b-59e2-ac72-bbb6540e1bda","slug":"lck","display_name":"LCK","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f1d38046-6772-515b-9276-9b38748ae601","slug":"ptprc","display_name":"PTPRC","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7a4df9a1-d64b-56ca-aada-ed349e74008d","slug":"lck-activation","display_name":"LCK activation competence","entity_type_key":"cellular_process"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"T-cell and biochemical assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Biochemical LCK/CD45 phosphorylation assays; CD45-deficient cells and LCK binding/phosphorylation experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Net effect depends on concentration/localization and both sites; no selenium-dependent site effect established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mammalian biochemical and T-cell systems","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9e42edb0-5a93-522a-83cd-054b88feaad4","evidence_kind":"curated_literature_summary","locator":"lines 1275-1286","start_line":1275,"end_line":1286,"excerpt":"## cd45-y505\n\nRemoving the Y505 phosphate can release LCK inhibition.\n\nCD45 removal of inhibitory LCK Y505 phosphorylation can favor an open activation-competent state.\n\nOrganism: Mammalian biochemical and T-cell systems\nCell type: T-cell and biochemical assays\nExperimental model: Biochemical LCK/CD45 phosphorylation assays; CD45-deficient cells and LCK binding/phosphorylation experiments\nLimitations: Net effect depends on concentration/localization and both sites; no selenium-dependent site effect established.\nPrimary reference: [The noncatalytic domains of Lck regulate its dephosphorylation by CD45](https://pubmed.ncbi.nlm.nih.gov/12922168/)\nPrimary reference: [CD45 specifically modulates binding of Lck to a phosphopeptide encompassing the negative regulatory tyrosine of Lck.](https://pubmed.ncbi.nlm.nih.gov/8428589/)","model_system":"Biochemical LCK/CD45 phosphorylation assays; CD45-deficient cells and LCK binding/phosphorylation experiments","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[{"id":"5e366951-a1de-580f-8598-7a25d70d63db","title":"CD45 effects at LCK Y394 and Y505 are reversed","kind":"contradiction","status":"corrected","why":"Removing inhibitory Y505 phosphate can permit activation; removing activating Y394 phosphate reduces it.","resolution":"Switch site effects and retain context-dependent dual regulation; no selenium-specific site effect established.","created_at":"2026-09-17 07:19:34","record_type":"correction","display_label":"Correction history","record_url":"/corrections/5e366951-a1de-580f-8598-7a25d70d63db","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1598,"end_line":1604,"papers":[{"paper_key":"cd45-2003","title":"The noncatalytic domains of Lck regulate its dephosphorylation by CD45","url":"https://pubmed.ncbi.nlm.nih.gov/12922168/","doi":"10.1016/S1570-9639(03)00190-0","year":2003,"model":"Biochemical LCK/CD45 phosphorylation assays","summary":"CD45 removes inhibitory Y505 and activating Y394 phosphate; effects differ by site."},{"paper_key":"sieh-1993","title":"CD45 specifically modulates binding of Lck to a phosphopeptide encompassing the negative regulatory tyrosine of Lck.","url":"https://pubmed.ncbi.nlm.nih.gov/8428589/","doi":"10.1002/j.1460-2075.1993.tb05659.x","year":1993,"model":"CD45-deficient cells and LCK binding/phosphorylation experiments","summary":"Supports release of LCK Y505-mediated inhibition."}]},"sides":[{"conflict_id":"5e366951-a1de-580f-8598-7a25d70d63db","ordinal":0,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":60,"end_line":60,"quote":"| **CD45** (PTPRC)                           | Cys828 | activates LCK (Y394) / inhibits (Y505)    |","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"5e366951-a1de-580f-8598-7a25d70d63db","ordinal":1,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1598,"end_line":1604,"quote":"## CD45 effects at LCK Y394 and Y505 are reversed\n\nRemoving inhibitory Y505 phosphate can permit activation; removing activating Y394 phosphate reduces it.\n\nSwitch site effects and retain context-dependent dual regulation; no selenium-specific site effect established.\nPrimary reference: [The noncatalytic domains of Lck regulate its dephosphorylation by CD45](https://pubmed.ncbi.nlm.nih.gov/12922168/)\nPrimary reference: [CD45 specifically modulates binding of Lck to a phosphopeptide encompassing the negative regulatory tyrosine of Lck.](https://pubmed.ncbi.nlm.nih.gov/8428589/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"Removing the Y505 phosphate can release LCK inhibition.","evidence_scope":"direct_experimental","papers":[{"key":"sieh-1993","title":"CD45 specifically modulates binding of Lck to a phosphopeptide encompassing the negative regulatory tyrosine of Lck.","url":"https://pubmed.ncbi.nlm.nih.gov/8428589/","doi":"10.1002/j.1460-2075.1993.tb05659.x","year":1993,"model":"CD45-deficient cells and LCK binding/phosphorylation experiments","summary":"Supports release of LCK Y505-mediated inhibition."},{"key":"cd45-2003","title":"The noncatalytic domains of Lck regulate its dephosphorylation by CD45","url":"https://pubmed.ncbi.nlm.nih.gov/12922168/","doi":"10.1016/S1570-9639(03)00190-0","year":2003,"model":"Biochemical LCK/CD45 phosphorylation assays","summary":"CD45 removes inhibitory Y505 and activating Y394 phosphate; effects differ by site."}]}}