MOLECULAR BIOLOGY OF THE GENES ENCODING PROHORMONES FOR BOMBESIN-LIKE PEPTIDES

这个项目的目标是了解结构的各个方面， 编码哺乳动物对应物的基因的功能和调节 到蛙皮素样神经肽。两种哺乳动物蛙皮素样肽具有 迄今为止，已鉴定出胃泌素释放肽（MP）和神经介肽B （NM-B）。这两种肽都存在于中枢和外周神经系统的亚群中。 神经元，并在其羧基末端结构域共享结构基序， 其对于结合高亲和力细胞是必需且充分的 蛙皮素受体有几个子项目正在积极 进行：1）大鼠和人prepro-GRP的cDNA和基因组克隆， 已经分离并表征了前原-NMB基因以鉴定 启动子区域中的潜在调控基序。2)原位 杂交技术被用来确定 GRP和NMB mRNA在脑细胞水平的表达; 3）启动子-报告基因 基因构建体将被引入培养的细胞宿主， 转染以定位人GRP启动子区中的元件 负责细胞类型特异性调节的基因。

The goal of this project is to understand aspects of the structure, function, and regulation of the genes encoding the mammalian counterparts to bombesin-like neuropeptides. Two mammalian bombesin-like peptides have been identified to date, gastrin-releasing peptide (MP and neuromedin B (NM-B). Both peptides are found in a subset of central and peripheral neurons, and share a structural motif at their carboxyl-terminal domains, which is necessary and sufficient for binding to high-affinity cell surface bombesin receptors. There are several subprojects being actively pursued: 1) CDNA and genomic clones for rat and human prepro-GRP and prepro-NMB genes have been isolated and characterized to identify potential regulatory motifs in the promoter regions. 2) in situ hybridization techniques are being utilized to determine the localization of GRP and NMB mRNA at the cellular level in brain; 3) Promoter-reporter gene constructs will be introduced into cultured cell hosts by transfection to map the elements in the promoter region of the human GRP gene responsible for the cell-type specific regulation.