DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation

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DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation
Sun Young Kim; Y M Han; Mihee OhWon-Kon KimKyoung Jin OhSang Chul LeeKwang-Hee BaeBaek Soo Han
Bibliographic Citation
Stem Cells and Development, vol. 24, no. 6, pp. 686-700
Publication Year
Protein 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.
Mary Ann Liebert, Inc
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Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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