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Physiological roles of GTP binding protein associated with pertussis toxin (IAP) for the study of medicinal and diagnostic functions

与百日咳毒素 (IAP) 相关的 GTP 结合蛋白在医学和诊断功能研究中的生理作用

基本信息

批准号：
61870093
负责人：
TOKUMITSU Yukiko
金额：
$ 8.96万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

Many kinds of hormones and neurotransmitters interact with their specific receptors coupled to guanine nucleotide-binding protein (G protein) and lead to physiological actions. Pertussis toxin (IAP) lose their function of G protein in various types of cells. IAP is a useful probe to study the mechanism of signal transduction via G protein. Therefore, we examined the roles of G protein serving as IAP substrates and other G protein. The results obtained were as follows. (1) Serum-induced DNA synthesis in 3T3 fibroblasts was inhibited via loss of function of IAP substrates, thereby leading to cell proliferation. (2) IAP-sensitive G protein plays a role in c-myc gene expression of rat hepatocytes. (3) A new G protein sensitive to IAP was induced during differentiation of HL-60 cells into neutrophil type of cells. (4) IAP inhibited differentiation of 3T3L1 cells into adipocytes via IAP-sensitive G protein. (5) One of two types of the P2-purinergic receptors was coupled to IAP-sensitive G protein, resulting in inhibition of cAMP formation. (6) Adenylate cyclase activity in NIH-3T3^<src> cells decreased via reduction of the number of beta-adrenoceptors and phosphorylation of Gs protein but not ADP-ribosylation of Gi or Go. (7) Thrombin and epinephrine in platelets activated phospholipase A2 via IAP-sensitive G protein. (8) Adenylate cyclase activity in NIH-3T3^<ras> cells increased via rbduction of the amount of IAP-sensitive G protein. (9) Purified muscarinic receptors were coupled to purified IAP-sensitive G protein reconstituted. (10) Serotonin 1A receptors were coupled to IAP-sensitive G protein in rat brain cortex and hippocampus. (11) Amino acid sequences were determined, and GTP-binding sites and ADP-ribosylation sites were identified by molecular cloning of rat brain Gi and Go cDNA.

许多激素和神经递质与它们的特异性受体结合在鸟嘌呤核苷酸结合蛋白（G蛋白）上，从而产生生理作用。百日咳毒素（Pertussis toxin，IAP）在多种细胞中失去G蛋白的功能。IAP是研究G蛋白介导的信号转导机制的有效探针。因此，我们研究了作为IAP底物的G蛋白和其他G蛋白的作用。获得的结果如下。(1)血清诱导的3 T3成纤维细胞中的DNA合成通过IAP底物的功能丧失而被抑制，从而导致细胞增殖。(2)IAP敏感性G蛋白在大鼠肝细胞c-myc基因表达中的作用(3)在HL-60细胞向中性粒细胞分化的过程中，诱导出一种对IAP敏感的新G蛋白。(4)IAP通过IAP敏感的G蛋白抑制3 T3 L1细胞向脂肪细胞的分化。(5)两种类型的P2-嘌呤能受体之一与IAP敏感的G蛋白偶联，导致cAMP形成的抑制。(6)NIH-3 T3 ^细胞中腺苷酸环化酶活性<src>通过β-肾上腺素受体数量减少和Gs蛋白磷酸化而降低，但不通过Gi或Go的ADP核糖基化。(7)血小板中的凝血酶和肾上腺素通过IAP敏感的G蛋白激活磷脂酶A2。(8)NIH-3 T_（3+）细胞腺苷酸环化酶活性<ras>通过诱导IAP敏感性G蛋白表达而升高。(9)纯化的毒蕈碱受体偶联到纯化的IAP敏感性G蛋白重建。(10)5-羟色胺1A受体与大鼠大脑皮层和海马的IAP敏感性G蛋白偶联。(11)氨基酸序列进行了测定，并确定GTP结合位点和ADP核糖基化位点的大鼠脑Gi和Go cDNA的分子克隆。