{"corpus_id":22873580,"paper_sha":"adbe9571b9505ccafd997514c066baa2c50cc1c0","doi":"10.1074/JBC.M403172200","arxiv_id":null,"pmid":15659400,"pmcid":null,"mag_id":2065778432,"dblp_id":null,"acl_id":null,"title":"Activation of the Trk Signaling Pathway by Extracellular Zinc","year":2005,"publication_date":"2005-03-25","venue":"Journal of Biological Chemistry","journal":{"name":"Journal of Biological Chemistry","pages":"11995 - 12001","volume":"280"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":1,"citation_count":204,"influential_citation_count":11,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Brain-Derived Neurotrophic Factor","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D019208"},{"d":"Metalloproteases","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D045726"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Neuronal Plasticity","mj":false,"ui":"D009473"},{"d":"Phosphorylation","mj":false,"ui":"D010766"},{"d":"Receptor, trkB","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D020813"},{"d":"Signal Transduction","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D015398"},{"d":"Synapses","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D013569"},{"d":"Zinc","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D015032"}],"chemicals":[{"n":"Brain-Derived Neurotrophic Factor","ui":"D019208","reg":"0"},{"n":"Receptor, trkB","ui":"D020813","reg":"EC 2.7.10.1"},{"n":"Metalloproteases","ui":"D045726","reg":"EC 3.4.-"},{"n":"Zinc","ui":"D015032","reg":"J41CSQ7QDS"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.jbc.org/article/S0021925820809119/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/adbe9571b9505ccafd997514c066baa2c50cc1c0","s2_open_access_license":"CCBY","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"In certain brain regions, extracellular zinc concentrations can rise precipitously as intense neuronal activity releases large amounts of zinc from the nerve terminals. Although zinc release has been suggested to play a pathological role, its precise physiological effect is poorly understood. Here, we report that exposure to micromolar quantities of zinc for only a few minutes robustly and specifically activated tropomyosin-related kinase (Trk) receptors, most likely TrkB, in cultured cortical neurons. We further found that Trk activation by zinc is extracellularly mediated by activation of metalloproteinases, which release pro-BDNF from cells and convert pro-BDNF to mature BDNF. These results suggest that activity-dependent release of extracellular zinc leads to metalloproteinase activation, which plays a critically important role in Trk receptor activation at zinc-containing synapses.","claims":[{"public_id":"cl_32e1d813b579c65e63834fe34f73a308","status":"active","text":"Activity-dependent release of extracellular zinc leads to metalloproteinase activation, which plays a critically important role in Trk receptor activation at zinc-containing synapses.","confidence":0.9,"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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of brain-derived neurotrophic factor produced by conversion of pro-BDNF via metalloproteinases.","types":["protein","signaling molecule"],"aliases":["BDNF"],"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_9b4d1514fef3b68a934e79f9a78cfb2a"},{"public_id":"co_bd3d1802608fa8115b22204e5f825d39","status":"active","name":"zinc","description":"Extracellular zinc ions that can rise precipitously in certain brain regions following intense neuronal activity.","types":["chemical","signaling molecule"],"aliases":[],"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 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