| ○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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| ○著者 (必須): | 1. | (英) Sekiguchi Mari (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) Shigeri Yasushi (日) (読)
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| 5. | (英) Sueyoshi Noriyuki (日) (読)
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| 6. | (英) Kameshita Isamu (日) (読)
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| ○題名 (必須): | □ | (英) Identification of amphiphysin 1 as an endogenous substrate for CDKL5, a protein kinase associated with X-linked neurodevelopmental disorder. (日)
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| ○要約 (任意): | □ | (英) Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase predominantly expressed in brain and mutations of its gene are known to be associated with neurodevelopmental disorders such as X-linked West syndrome and Rett syndrome. However, the physiological substrates of CDKL5 that are directly linked to these neurodevelopmental disorders are currently unknown. In this study, we explored endogenous substrates for CDKL5 in mouse brain extracts fractionated by a liquid-phase isoelectric focusing. In conjunction with CDKL5 phosphorylation assay, this approach detected a protein band with an apparent molecular mass of 120kDa that is remarkably phosphorylated by CDKL5. This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293. The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis. Introduction of point mutations in the catalytic domain of CDKL5, which are disease-causing missense mutations found in Rett patients, resulted in the impairment of kinase activity toward Amph1. These results suggest that Amph1 is the cytoplasmic substrate for CDKL5 and that its phosphorylation may play crucial roles in the neuronal development. (日)
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| ○キーワード (推奨): | 1. | (英) Amino Acid Sequence (日) (読)
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| 2. | (英) Animals (日) (読)
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| 3. | (英) Brain (日) (読)
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| 4. | (英) Isoelectric Focusing (日) (読)
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| 5. | (英) Male (日) (読)
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| 6. | (英) Mice (日) (読)
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| 7. | (英) Molecular Sequence Data (日) (読)
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| 8. | (英) Mutation (日) (読)
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| 9. | (英) Nerve Tissue Proteins (日) (読)
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| 10. | (英) Phosphorylation (日) (読)
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| 11. | (英) Protein Binding (日) (読)
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| 12. | (英) Protein-Serine-Threonine Kinases (日) (読)
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| 13. | (英) Rett Syndrome (日) (読)
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| 14. | (英) Serine (日) (読)
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| 15. | (英) Tissue Extracts (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Archives of Biochemistry and Biophysics ([Elsevier])
(pISSN: 0003-9861, eISSN: 1096-0384)
| ○ISSN (任意): | □ | 1096-0384
ISSN: 0003-9861
(pISSN: 0003-9861, eISSN: 1096-0384) Title: Archives of biochemistry and biophysicsTitle(ISO): Arch Biochem BiophysPublisher: Academic Press Inc. (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 535
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| ○号 (必須): | □ | 2
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| ○頁 (必須): | □ | 257 267
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2013年 5月 4日 (平成 25年 5月 4日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1016/j.abb.2013.04.012 (→Scopusで検索)
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| ○PMID (任意): | □ | 23651931 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) PublicationType: Journal Article (日)
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| 2. | (英) PublicationType: Research Support, Non-U.S. Gov't (日)
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