| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Oi Ami (日) (読)
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| 2. | 片山 将一 ([徳島大学.大学院医歯薬学研究部.薬学域.先端薬学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.生命薬学系.医薬品病態生化学])
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| 3. | (英) Hatano Naoya (日) (読)
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| 4. | (英) Sugiyama Yasunori (日) (読)
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| 5. | (英) Kameshita Isamu (日) (読)
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| 6. | (英) Sueyoshi Noriyuki (日) (読)
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| ○題名 (必須): | □ | (英) Subcellular distribution of cyclin-dependent kinase-like 5 (CDKL5) is regulated through phosphorylation by dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). (日)
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| ○副題 (任意): |
| ○要約 (任意): | □ | (英) Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase primarily expressed in the central nervous system and is known to cause X-linked neurodevelopmental disorders such as Rett syndrome. However, the mechanisms regulating CDKL5 have not yet been fully clarified. Therefore, in this study, we investigated the protein kinase that directly phosphorylates CDKL5, identifying it as dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), an enzyme binding to and phosphorylating CDKL5. We showed that subcellular distribution of CDKL5 was regulated by its phosphorylation by DYRK1A. In mouse neuroblastoma Neuro2a cells, CDKL5 was localized in both the cytosol and nucleus, whereas DYRK1A showed a typical nuclear localization. When CDKL5 and DYRK1A were co-expressed, the cytosolic localization of CDKL5 was significantly increased. Results of site-directed mutagenesis revealed that the phosphorylation site was Ser-308, in the vicinity of the nuclear localization signal. A mutation mimicking the phosphorylated serine residue by aspartate substitution (S308D) changed CDKL5 localization to the cytosol, whereas the corresponding alanine-substituted analog, CDKL5(S308A), was primarily localized to the nucleus. Taken together, these results strongly suggested that DYRK1A bound to CDKL5 and phosphorylated it on Ser-308, thus interfering with its nuclear localization. (日)
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| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | (英) Cell Line (日) (読)
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| 3. | (英) Enzyme Activation (日) (読)
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| 4. | (英) Gene Expression Regulation, Enzymologic (日) (読)
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| 5. | (英) Mice (日) (読)
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| 6. | (英) Neurons (日) (読)
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| 7. | (英) Phosphorylation (日) (読)
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| 8. | (英) Protein-Serine-Threonine Kinases (日) (読)
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| 9. | (英) Protein-Tyrosine Kinases (日) (読)
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| 10. | (英) Subcellular Fractions (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Biochemical and Biophysical Research Communications ([Elsevier])
(pISSN: 0006-291X, eISSN: 1090-2104)
| ○ISSN (任意): | □ | 1090-2104
ISSN: 0006-291X
(pISSN: 0006-291X, eISSN: 1090-2104) Title: Biochemical and biophysical research communicationsTitle(ISO): Biochem Biophys Res CommunPublisher: Elsevier B.V. (NLM Catalog)
(Scopus)
(CrossRef)
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| ○巻 (必須): | □ | 482
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| ○号 (必須): | □ | 2
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| ○頁 (必須): | □ | 239 245
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2016年 11月 11日 (平成 28年 11月 11日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1016/j.bbrc.2016.11.048 (→Scopusで検索)
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| ○PMID (任意): | □ | 27840050 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) PublicationType: Journal Article (日)
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