THE MOLECULAR BIOLOGY OF THE MAMMALIAN GRP GENE

胃泌素释放肽（GRP）是一种由27个氨基酸组成的神经肽， 两栖动物十四肽蛙皮素的哺乳动物同系物（1）。 的 哺乳动物GRP的羧基末端14个氨基酸残基非常 类似于两栖类铃蟾肽，特别是末端七肽， 似乎是分子的生物活性区域， 对结合受体至关重要（2）。 蛙皮素/GRP已被检测到， 哺乳动物脑（3）以及肠的外周神经细胞（4），其中 已知其刺激胃中G细胞释放胃泌素 狗和人的粘膜。 此外，蛙皮素/GRP已被检测到， 正常支气管上皮的肺内分泌细胞（5），以及 如肺类癌（6，7）和人小细胞肺癌（SCLC） （8、9、10）。 在一定的条件下，GRP可以刺激人小细胞肺癌的生长 细胞系（11，12）、正常人支气管上皮细胞（13）和小鼠 Swiss 3 T3细胞（14），其促生长特性似乎 由细胞表面受体介导（15）。 GRP是合成的， 由一些SCLC细胞系分泌并且还可以刺激细胞生长， 表明这种神经肽可能作为自分泌生长因子发挥作用 这有助于SCLC的转化生长特性（12）。 我们的小组集中注意力通过探索 前原GRP基因的分子生物学。 作为第一步 分析，我们从几个不同的组织中获得了约25个GRP cDNA克隆， 人SCLC cDNA文库。 分析这些 克隆揭示了前原GRP翻译产物，其由信号 序列，预测的27个氨基酸的GRP神经肽，和一种新的 GRP-相关肽代表糖蛋白的羧基部分， 翻译阅读框架编码GRP（16，17）。

Gastrin releasing peptide (GRP), a 27 amino acid neuropeptide is a mammalian homologue of the amphibian tetradecapeptide bombesin (1). The carboxy terminal fourteen amino acid residues of mammalian GRP are very similar to amphibian bombesin, particularly the terminal heptapeptide which appears to be the biologically active region of the molecule that is critical for binding to receptors (2). Bombesin/GRP has been detected in mammalian brain (3) and also in peripheral nerve cells of the gut (4) where it is known to stimulate the release of gastrin from G cells in the gastric mucosa in dogs and humans. In addition, bombesin/GRP has been detected in the pulmonary endocrine cells of normal bronchial epithelium (5), as well as in lung carcinoid tumors (6,7) and human small cell lung cancer (SCLC) (8,9,10). Under certain circumstances, GRP can stimulate the growth of human SCLC cell lines (11,12), normal human bronchial epithelial cells (13), and mouse Swiss 3T3 cells (14) where its growth promoting properties appear to be mediated by a cell surface receptor (15). GRP is both synthesized and secreted by some SCLC cell lines and can also stimulate cell growth, indicating this neuropeptide may function as an autocrine growth factor that contributes to the transformed growth properties of SCLC (12). Our group focused its attention on extending these studies by exploring the molecular biology of the pre-pro GRP gene. As a first step in this analysis, we obtained a collection of about 25 GRP cDNA clones from several human SCLC cDNA libraries generated in this laboratory. Analysis of these clones revealed a pre-pro GRP translation product consisting of a signal sequence, the predicted 27 amino acid GRP neuropeptide, and a novel GRP-associated peptide representing the carboxy portion of the translational reading frame encoding GRP (16,17).