DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, SK | ko |
dc.contributor.author | Park, HJ | ko |
dc.contributor.author | Hong, HS | ko |
dc.contributor.author | Baik, EJ | ko |
dc.contributor.author | Jung, MW | ko |
dc.contributor.author | Mook-Jung, I | ko |
dc.date.accessioned | 2013-03-08T13:56:12Z | - |
dc.date.available | 2013-03-08T13:56:12Z | - |
dc.date.created | 2013-02-21 | - |
dc.date.created | 2013-02-21 | - |
dc.date.issued | 2005-11 | - |
dc.identifier.citation | FASEB JOURNAL, v.19, pp.157 - + | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://hdl.handle.net/10203/93180 | - |
dc.description.abstract | As an essential protease in the generation of amyloid beta, gamma-secretase is believed to play an important role in the pathogenesis of Alzheimer's disease. Although a great deal of progress has been made in identifying the components of.-secretase complex, the endogenous regulatory mechanism of gamma-secretase is unknown. Here we show that gamma-secretase is endogenously regulated via extracellular signal regulated MAP kinase (ERK) 1/2-dependent mitogen-activated protein kinase (MAPK) pathway. The inhibition of ERK1/2 activity, either by a treatment with a MEK inhibitor or an ERK knockdown transfection, dramatically increased gamma-secretase activity in several different cell types. JNK or p38 kinase inhibitors had little effect, indicating that the effect is specific to ERK1/2-dependent MAPK pathway. Conversely, increased ERK1/2 activity, by adding purified active ERK1/2 or EGF-induced activation of ERK1/2, significantly reduced gamma-secretase activity, demonstrating down-regulation of gamma-secretase activity by ERK1/2. Whereas gamma-secretase expression was not affected by ERK1/ 2, its activity was enhanced by phosphatase treatment, indicating that ERK1/2 regulates gamma-secretase activity by altering the pattern of phophorylation. Among the components of isolated gamma-secretase complex, only nicastrin was phosphorylated by ERK1/2, and it precipitated with ERK1/2 in a co-immunoprecipitation assay, which suggests binding between ERK1/ 2 and nicastrin. Our results show that ERK1/ 2 is an endogenous regulator of gamma-secretase, which raises the possibility that ERK1/2 down-regulates gamma-secretase activity by directly phosphorylating nicastrin. | - |
dc.language | English | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.subject | AMYLOID PRECURSOR PROTEIN | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | SIGNAL-TRANSDUCTION | - |
dc.subject | BETA-SECRETASE | - |
dc.subject | MAP KINASE | - |
dc.subject | HUMAN BRAIN | - |
dc.subject | IN-VIVO | - |
dc.subject | INTRAMEMBRANE PROTEOLYSIS | - |
dc.subject | GLYCOSYLATED NICASTRIN | - |
dc.subject | INTRACELLULAR DOMAIN | - |
dc.title | ERK1/2 is an endogenous negative regulator of the gamma-secretase activity | - |
dc.type | Article | - |
dc.identifier.wosid | 000234053100007 | - |
dc.identifier.scopusid | 2-s2.0-30744453036 | - |
dc.type.rims | ART | - |
dc.citation.volume | 19 | - |
dc.citation.beginningpage | 157 | - |
dc.citation.endingpage | + | - |
dc.citation.publicationname | FASEB JOURNAL | - |
dc.identifier.doi | 10.1096/fj.05-4055fje | - |
dc.contributor.localauthor | Jung, MW | - |
dc.contributor.nonIdAuthor | Kim, SK | - |
dc.contributor.nonIdAuthor | Park, HJ | - |
dc.contributor.nonIdAuthor | Hong, HS | - |
dc.contributor.nonIdAuthor | Baik, EJ | - |
dc.contributor.nonIdAuthor | Mook-Jung, I | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Alzheimer&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | amyloid beta | - |
dc.subject.keywordAuthor | nicastrin | - |
dc.subject.keywordPlus | AMYLOID PRECURSOR PROTEIN | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | SIGNAL-TRANSDUCTION | - |
dc.subject.keywordPlus | BETA-SECRETASE | - |
dc.subject.keywordPlus | MAP KINASE | - |
dc.subject.keywordPlus | HUMAN BRAIN | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | INTRAMEMBRANE PROTEOLYSIS | - |
dc.subject.keywordPlus | GLYCOSYLATED NICASTRIN | - |
dc.subject.keywordPlus | INTRACELLULAR DOMAIN | - |
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