A Cell Genetic Study on the Molecular Mechanism of Hormone Receptor Systems

激素受体系统分子机制的细胞遗传学研究

• 批准号: 59440086
• 负责人: SHIMIZU Nobuyoshi
• 金额: $ 16万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1984
• 资助国家: 日本
• 起止时间: 1984 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-59440086/
• 关键词: EGF; Insulin; Receptor; Tumor Promoter; Immunotoxin; Signal Transfer; Cキナーゼ; 膜レセプター; 細胞増殖因子; 体細胞遺伝学

Epidermal growth factor (EGF) and insulin interact with their own membrane receptors and regulate cellular metabolism and growth through generating mitogenic and hormonal signals. In order to facilitate the studies on the mechanisms of signal transduction, we have taken a cell genetic approach and devised selection procedures by which to isolate cell variants that are defective or extraordinary in their response. These include the use of toxic hybrid hormones, immunotoxin and mitotic shake-off techniques. Several series of genetic variants have been isolated. The characteristics of the insulin-diphtheria toxin A fragment-resistant variants provided genetic evidence for the divergence of the insulin receptor-mediated mitogenic and hormonal signals during the post-receptor pathways which is apparently regulated by the insulin-dependent phosphorylation. Also, the analysis of dihydroteleocidin B-nonresponsive variants suggested that phosphatidylinositol turnover followed by protein kinase C activation is not sufficient for mitogenic stimulation and that the coordination of the protein kinase C system with the growth factor receptor system may be necessary for full mitogenic response. Chromosomal mapping of human genes related to EGF receptor and multi-drug resistance has also been carried out.

表皮生长因子（EGF）和胰岛素与自身的膜受体相互作用，通过产生有丝分裂和激素信号来调节细胞代谢和生长。为了促进对信号转导机制的研究，我们采用了细胞遗传学方法并设计了选择程序，通过该程序分离出有缺陷或异常反应的细胞变体。这些方法包括使用有毒的杂交激素、免疫毒素和有丝分裂脱落技术。已经分离出了几个系列的遗传变异。胰岛素-白喉毒素A片段抗性变异的特征为胰岛素受体介导的有丝分裂和激素信号在受体后通路中的分化提供了遗传证据，这显然是由胰岛素依赖性磷酸化调节的。此外，对二氢远杀蛋白b无应答变异的分析表明，磷脂酰肌醇转换后的蛋白激酶C激活不足以刺激有丝分裂，蛋白激酶C系统与生长因子受体系统的协调可能是充分的有丝分裂反应所必需的。人类EGF受体和多药耐药相关基因的染色体定位也已开展。

项目成果

Shimizu,Y.: J.Biol.Chem.261. 7342-7346 (1986)

清水，Y.：J.Biol.Chem.261。

Shimizu, Nobuyoshi: "Cell Genetic Analysis of the Receptor Systems for Bioactive Polypeptides" Receptors and Recognition. 16. 109-142 (1984)

Shimizu，Nobuyoshi：“生物活性多肽受体系统的细胞遗传学分析”受体和识别。

Shimizu,Y.: Cancer Res.46. 4027-4031 (1986)

Shimizu,Y.：癌症研究 46。

Somat.Cell Mol.Genet.11-5. (1985)

体细胞分子遗传学11-5。

Shimizu,N.: Cell Struct.Funct.9. 203-212 (1984)

Shimizu,N.：细胞结构.功能.9。