A study for gene expression of synthetic enzymes and receptors for lipid biofactors

脂质生物因子合成酶和受体基因表达的研究

• 批准号: 05304027
• 负责人: ICHIKAWA Atsushi
• 金额: $ 19.97万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05304027/
• 关键词: PAF acetylhydrolase; P450 (11beta, aldo); cyclooxygenase; aldosterone synthetase; PGE2 receptor subtypes; 1alpha, 25-dihydroxyvitamin D3-24-hydroxylase; midkine; PAF receptor; P450(11β,aldo); シクロオキシゲナーゼ-2(COX-2); コルチコステロン合成酵素; PGE_2受容体サブタイプ; 1

The project has intended to research in molecular structures and functions of rate-limiting enzymes in the synthesis, and receptors/signal transduction systems in the biological activities for various bioactive lipid modulators ; prostaglandins, PAF,steroid hormones, and vitamin A and D.Summary obtained by research groups as below ;(1) Prostaglandins and PAF group ; cDNA cloning and its expression & purification of 12-lipoxygenase, Induction of prostaglandin H synthase-2 and 12-lipoxygenase by cytokinines or prostagalndins (by Yamamoto) . cDNA cloning and expression of PAF acetylhydrolase, and identification of its alpha subunit of enzyme encoding Miller-Dieker lissencephaly (by Inoue) . cDNA cloning and tissue distribution, and its gene expression and signal transduction of PAF (by Shimizu) , and of 5 basic prostaglandin receptor types (DP,EP,FP,IP,TP) , 4EP subtypes and 3 EPs isoforms (by Narumiya & Ichikawa) . (2) Steroid hormone group ; Regulation of steroid 11beta/18-hydroxylation and aldosterone production, and Isolation and characterization of three CYP11B genes, comprising 11beta-hydroxylase, aldosterone synthetase and a novel genes, analysis of promoter regions of CYP11B genes (by Ishimura & Okamoto) . Expression and tissue specific localization of Ad4BP,a steroidgenic cell-specific transcription factor (by Morohashi) . (3) Vitamins A & D group ; Isolation and characterization, expression and tissue distribution of retinoic acid responsive gene product, midkine, growth/differentiation factor of various tissues (by Muramatsu) . Regulation of mRNA expression, and Identification of vitamin D responsive element in the 5'-flanking region of 1alpha, 25-dihydroxyvitamin D3-24-hydroxylase (by Suda)

本项目旨在研究前列腺素、前列腺素F、类固醇激素、维生素A和D的合成中限速酶的分子结构和功能，以及各种生物活性脂类调节剂的受体/信号转导系统。研究小组获得的综述如下：(1)前列腺素和PAF组；12-脂氧合酶的cDNA克隆及其表达和纯化；细胞分裂素或前列腺素诱导前列腺素H合成酶-2和12-脂氧合酶的表达和纯化(山本)。PAF乙酰水解酶基因的克隆、表达及其编码Miller-Dieker脑白质酶α亚基的鉴定(井上)。PAF(清水)、5种基本前列腺素受体类型(DP、EP、FP、IP、TP)、4种EP亚型和3种EPs亚型(Narumiya&Ichikawa)的基因克隆、组织分布、基因表达和信号转导。(2)类固醇激素组；类固醇11β/18-羟基化和醛固酮合成的调节；3个CYP11B基因的分离和鉴定，包括11β-羟基酶、醛固酮合成酶和1个新基因；类固醇细胞特异性转录因子Ad4BP的表达和组织特异性定位(Morohashi)。(3)维生素A和维生素D组：维甲酸应答基因产物、中期因子、各种组织的生长分化因子的分离鉴定、表达和组织分布(村松)。1α，25-二羟基维生素D3-24-羟基酶5‘侧翼区基因表达调控及维生素D反应元件的鉴定(苏达)

项目成果

Takano Tomoko: "Role of cytoplasmic-tail phosphorylation sites of plateletactivating factor receptor in agonist-induced desensitization." J. Biol. Chem.269. 22453-22458 (1994)

Takano Tomoko：“血小板活化因子受体胞质尾部磷酸化位点在激动剂诱导的脱敏中的作用。”

Suzuki,H.: "Site-directed mutagenesis analysis of arachidonate 12-lipoxygenase of porcine leukocytes" Biochimica et Biophysica Acta. (in press). (1994)

Suzuki,H.：“猪白细胞花生四烯酸 12-脂氧合酶的定点诱变分析”Biochimica et Biophysicala Acta。

Nusing,RM.: "Characterization and chromosomal mapping of the human thromboxane-A_2 receptor gene" The Journal of Biological Chemistry. 268. 25253-25259 (1993)

Nusing,RM.：“人类血栓素-A_2 受体基因的表征和染色体图谱”《生物化学杂志》。

Morohashi Ken-ichirou: "Functional difference between Ad4BP and ELP, and their distributions in steroidogenic tissues." Mol. Endocrinol.8. 643-653 (1994)

Morohashi Ken-ichirou：“Ad4BP 和 ELP 之间的功能差异，以及它们在类固醇生成组织中的分布。”

Hattori Mitsuharu: "Cloning and expression of a cDNA encoding the β-subunit (30-kDa subunit) of bovine brain platelet activating factor acetylhydrolase." J. Biol. Chem.270. 31345-31352 (1995)

Hattori Mitsuharu：“编码牛脑血小板激活因子乙酰水解酶 β 亚基（30-kDa 亚基）的 cDNA 的克隆和表达。J. Biol. 31345-31352 (1995)。