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Characterization of human G2A : gene regulation and cellular function
https://doi.org/10.15083/00002330
https://doi.org/10.15083/00002330e27cac09-71e1-4b8c-8b2f-91adcfd20d75
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
41_57518.pdf (62.1 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-03-01 | |||||
| タイトル | ||||||
| タイトル | Characterization of human G2A : gene regulation and cellular function | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| ID登録 | ||||||
| ID登録 | 10.15083/00002330 | |||||
| ID登録タイプ | JaLC | |||||
| その他のタイトル | ||||||
| その他のタイトル | Gタンパク質共役型受容体G2A : 遺伝子発現および細胞内機能解析 | |||||
| 著者 |
村上, 尚加
× 村上, 尚加 |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 6542 | |||||
| 姓名 | ムラカミ, ナオカ | |||||
| 著者所属 | ||||||
| 著者所属 | 東京大学大学院医学系研究科分子細胞生物学専攻 | |||||
| Abstract | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | G-protein coupled receptors (GPCRs) play pivotal roles in almost all the physiological and pathological conditions. However, many of the receptors remain as “orphan” receptors, whose ligand(s) are unknown. G2A (named for G2 accumulation in cell cycle) was one of these orphan receptors, whose constitutive activity makes the identification of the ligand(s) difficult. The aim of this study is to identify the ligand(s) of hG2A and to characterize the cellular function of the receptor, through investigating the intracellular signaling and the transcriptional regulation.// The findings in this PhD thesis consist of two major parts. First, human G2A (hG2A) is activated by extracellular low pH, though it shows significant activity at physiological condition of pH 7.4 (constitutive activity). The pH-dependent activation evoked by hG2A is Rho-dependent, which is completely inhibited by C3-toxin, and partially by the expression of dominant negative Rho. Considering the structural homology with Ovarian cancer G-protein coupled receptor 1 (OGR1/GPR68), another member of G2A family, the acid-sensing ability is attributed to the conserved histidine residue H174, as H174F mutant exhibits less pH-dependent activity compared with wild type receptor. In addition, lysophosphatidylcholine (LPC), a proposed agonist for G2A, actually inhibited pH-dependent activity at IC50 of 3 μM. Second, transcriptional regulation of hG2A in THP-1, a monocytic cell line, is dependent both on the chromatin structure around the transcriptional start site (TSS), and on the transcription factors’ (c/EBPα and β, Runx1 and Pu.1) binding to their cis-elements, located at the core promoter just upstream of TSS. | |||||
| 書誌情報 | 発行日 2009-03-23 | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位 | ||||||
| 値 | doctoral | |||||
| 学位分野 | ||||||
| Medical Science (医学) | ||||||
| 学位授与機関 | ||||||
| 学位授与機関名 | University of Tokyo (東京大学) | |||||
| 研究科・専攻 | ||||||
| Department of Molecular Cell Biology, Graduate School of Medicine (医学系研究科分子細胞生物学専攻) | ||||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2009-03-23 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第24772号 | |||||
| 学位記番号 | ||||||
| 博医第3192号 | ||||||
