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Article: Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the trkb receptor

TitleBiochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the trkb receptor
Authors
Issue Date2014
Citation
Journal of Biological Chemistry, 2014, v. 289, n. 40, p. 27571-27584 How to Cite?
Abstract© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. 7,8-dihydroxyflavone (7,8-DHF), a newly identified small molecular TrkB receptor agonist, rapidly activates TrkB in both primary neurons and the rodent brain and mimics the physiological functions of the cognate ligand BDNF. Accumulating evidence supports that 7,8-DHF exerts neurotrophic effects in a TrkB-dependent manner. Nonetheless, the differences between 7,8-DHF and BDNF in activating TrkB remain incompletely understood. Here we show that 7,8-DHF and BDNF exhibit different TrkB activation kinetics in which TrkB maturation may be implicated. Employing two independent biophysical approaches, we confirm that 7,8-DHF interacts robustly with the TrkB extracellular domain, with a Kd of ∼10 nM. Although BDNF transiently activates TrkB, leading to receptor internalization and ubiquitination/degradation, in contrast, 7,8-DHF-triggered TrkB phosphorylation lasts for hours, and the internalized receptors are not degraded. Notably, primary neuronal maturation may be required for 7,8-DHF but not for BDNF to elicit the full spectrum of TrkB signaling cascades. Hence, 7,8-DHF interacts robustly with the TrkB receptor, and its agonistic effect may be mediated by neuronal development and maturation.
Persistent Identifierhttp://hdl.handle.net/10722/225061
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151

 

DC FieldValueLanguage
dc.contributor.authorLiu, Xia-
dc.contributor.authorObiany, Obiamaka-
dc.contributor.authorChan, Chi Bun-
dc.contributor.authorHuang, Junjian-
dc.contributor.authorXue, Shenghui-
dc.contributor.authorYang, Jenny J.-
dc.contributor.authorZeng, Fanxing-
dc.contributor.authorGoodman, Mark-
dc.contributor.authorYe, Keqiang-
dc.date.accessioned2016-04-18T11:16:40Z-
dc.date.available2016-04-18T11:16:40Z-
dc.date.issued2014-
dc.identifier.citationJournal of Biological Chemistry, 2014, v. 289, n. 40, p. 27571-27584-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/225061-
dc.description.abstract© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. 7,8-dihydroxyflavone (7,8-DHF), a newly identified small molecular TrkB receptor agonist, rapidly activates TrkB in both primary neurons and the rodent brain and mimics the physiological functions of the cognate ligand BDNF. Accumulating evidence supports that 7,8-DHF exerts neurotrophic effects in a TrkB-dependent manner. Nonetheless, the differences between 7,8-DHF and BDNF in activating TrkB remain incompletely understood. Here we show that 7,8-DHF and BDNF exhibit different TrkB activation kinetics in which TrkB maturation may be implicated. Employing two independent biophysical approaches, we confirm that 7,8-DHF interacts robustly with the TrkB extracellular domain, with a Kd of ∼10 nM. Although BDNF transiently activates TrkB, leading to receptor internalization and ubiquitination/degradation, in contrast, 7,8-DHF-triggered TrkB phosphorylation lasts for hours, and the internalized receptors are not degraded. Notably, primary neuronal maturation may be required for 7,8-DHF but not for BDNF to elicit the full spectrum of TrkB signaling cascades. Hence, 7,8-DHF interacts robustly with the TrkB receptor, and its agonistic effect may be mediated by neuronal development and maturation.-
dc.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.titleBiochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the trkb receptor-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M114.562561-
dc.identifier.pmid25143381-
dc.identifier.scopuseid_2-s2.0-84907546597-
dc.identifier.volume289-
dc.identifier.issue40-
dc.identifier.spage27571-
dc.identifier.epage27584-
dc.identifier.eissn1083-351X-

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