DUSP4 Regulates Neuronal Differentiation and Calcium Homeostasis by Modulating ERK1/2 Phosphorylation

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dc.contributor.authorKim, Sun Youngko
dc.contributor.authorHan, Yong-Mahnko
dc.contributor.authorOh, Miheeko
dc.contributor.authorKim, Won-Konko
dc.contributor.authorOh, Kyoung-Jinko
dc.contributor.authorLee, Sang Chulko
dc.contributor.authorBae, Kwang-Heeko
dc.contributor.authorHan, Baek-Sooko
dc.date.accessioned2015-04-08T07:03:18Z-
dc.date.available2015-04-08T07:03:18Z-
dc.date.created2015-03-30-
dc.date.created2015-03-30-
dc.date.issued2015-03-
dc.identifier.citationSTEM CELLS AND DEVELOPMENT, v.24, no.6, pp.686 - 700-
dc.identifier.issn1547-3287-
dc.identifier.urihttp://hdl.handle.net/10203/195858-
dc.description.abstractProtein tyrosine phosphatases have been recognized as critical components of multiple signaling regulators of fundamental cellular processes, including differentiation, cell death, and migration. In this study, we show that dual specificity phosphatase 4 (DUSP4) is crucial for neuronal differentiation and functions in the neurogenesis of embryonic stem cells (ESCs). The endogenous mRNA and protein expression levels of DUSP4 gradually increased during mouse development from ESCs to postnatal stages. Neurite outgrowth and the expression of neuron-specific markers were markedly reduced by genetic ablation of DUSP4 in differentiated neurons, and these effects were rescued by the reintroduction of DUSP4. In addition, DUSP4 knockdown dramatically enhanced extracellular signal-regulated kinase (ERK) activation during neuronal differentiation. Furthermore, the DUSP4-ERK pathway functioned to balance calcium signaling, not only by regulating Ca2+/calmodulin-dependent kinase I phosphorylation, but also by facilitating Cav1.2 expression and plasma membrane localization. These data are the first to suggest a molecular link between the MAPK-ERK cascade and calcium signaling, which provides insight into the mechanism by which DUSP4 modulates neuronal differentiation.-
dc.languageEnglish-
dc.publisherMARY ANN LIEBERT, INC-
dc.subjectACTIVATED PROTEIN-KINASE-
dc.subjectEMBRYONIC STEM-CELLS-
dc.subjectMAP KINASE-
dc.subjectTYROSINE PHOSPHATASES-
dc.subjectGENE-EXPRESSION-
dc.subjectNERVOUS-SYSTEM-
dc.subjectCA2+ CHANNELS-
dc.subjectGROWTH CONE-
dc.subjectTRANSCRIPTION-
dc.subjectSPECIFICITY-
dc.titleDUSP4 Regulates Neuronal Differentiation and Calcium Homeostasis by Modulating ERK1/2 Phosphorylation-
dc.typeArticle-
dc.identifier.wosid000350459100002-
dc.identifier.scopusid2-s2.0-84924365613-
dc.type.rimsART-
dc.citation.volume24-
dc.citation.issue6-
dc.citation.beginningpage686-
dc.citation.endingpage700-
dc.citation.publicationnameSTEM CELLS AND DEVELOPMENT-
dc.identifier.doi10.1089/scd.2014.0434-
dc.contributor.localauthorHan, Yong-Mahn-
dc.contributor.nonIdAuthorOh, Mihee-
dc.contributor.nonIdAuthorKim, Won-Kon-
dc.contributor.nonIdAuthorOh, Kyoung-Jin-
dc.contributor.nonIdAuthorLee, Sang Chul-
dc.contributor.nonIdAuthorBae, Kwang-Hee-
dc.contributor.nonIdAuthorHan, Baek-Soo-
dc.type.journalArticleArticle-
dc.subject.keywordPlusACTIVATED PROTEIN-KINASE-
dc.subject.keywordPlusEMBRYONIC STEM-CELLS-
dc.subject.keywordPlusMAP KINASE-
dc.subject.keywordPlusTYROSINE PHOSPHATASES-
dc.subject.keywordPlusGENE-EXPRESSION-
dc.subject.keywordPlusNERVOUS-SYSTEM-
dc.subject.keywordPlusCA2+ CHANNELS-
dc.subject.keywordPlusGROWTH CONE-
dc.subject.keywordPlusTRANSCRIPTION-
dc.subject.keywordPlusSPECIFICITY-
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