{"id":"c404f89b-3ecb-5cd2-b59b-83e03cbbab31","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:opc-ly294002","predicate":"decreases_in_recorded_experiment","statement":"The PI3K inhibitor ly294002 reduced the SA-associated mTOR phosphorylation increase.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"2c979a2a-407c-563e-b157-aa4deb00d61e","mechanism_event_label":"The PI3K inhibitor ly294002 reduced the SA-associated mTOR phosphorylation increase.","subject":{"id":"2e2e42db-847b-5248-b05a-ac5afed107b1","slug":"ly294002","display_name":"LY294002","entity_type_key":"small_molecule"},"object":{"id":"ba61bf20-8aff-5dab-a70f-19d7be965e84","slug":"rat-opc-mtor-phosphorylation","display_name":"Rat OPC mTOR phosphorylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2c979a2a-407c-563e-b157-aa4deb00d61e","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:opc-ly294002-event","event_type":"experimental_observation","label":"The PI3K inhibitor ly294002 reduced the SA-associated mTOR phosphorylation increase.","description":"**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2e2e42db-847b-5248-b05a-ac5afed107b1","slug":"ly294002","display_name":"LY294002","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"ly294002 plus SA","sequence_order":0,"notes":""},{"entity":{"id":"ba61bf20-8aff-5dab-a70f-19d7be965e84","slug":"rat-opc-mtor-phosphorylation","display_name":"Rat OPC mTOR phosphorylation","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"67ad4a8f-1bf6-59e5-90a6-97b7709024d3","slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"},"role":"joint exposure","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7fca1403-41f3-5b05-a6fa-b19bd9f7d3fc","slug":"rat-mtor","display_name":"Rat mechanistic target of rapamycin / Mtor","entity_type_key":"protein"},"role":"measured component","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text retrieved; relevant methods/results/figures reviewed. 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The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The PI3K inhibitor ly294002 reduced the SA-associated mTOR phosphorylation increase.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice. | 2019 | DOI 10.1007/s12264-018-0322-7 | PMID 30684125 | https://pubmed.ncbi.nlm.nih.gov/30684125/ | https://doi.org/10.1007/s12264-018-0322-7 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6527532/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 71-71; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3a2f068d-a207-5e29-92eb-0bdf9c055b13","evidence_kind":"source_excerpt","locator":"Lines 71-71","start_line":71,"end_line":71,"excerpt":"**Perturbations expose a conditional signaling route.** In those rat precursor cultures, rapamycin blocked the shikimic-acid-associated rise in MBP, while the MEK inhibitor U0126 did not abolish it. PI3K inhibitors wortmannin and LY294002 reduced the elevated mTOR-phosphorylation readout toward control. These are joint experimental contrasts supporting pathway dependence; they do not establish that shikimic acid binds mTOR or that all MEK activity is irrelevant. [Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice.](https://pubmed.ncbi.nlm.nih.gov/30684125/)","model_system":"Primary rat OPC joint pharmacological perturbation.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. 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