GASTROINTESTINAL SIGNIFICANCE OF GASTRIN REGULATION

描述(改编自申请人的摘要)：这是一项建议，以 胃泌素/CCK-B受体的特性和功能的继续研究 和推测的甘氨酸延伸胃泌素受体(G-Gly)。在上一次 在资助期内，派和他的合作者已经表明，甘氨酸延长了 中间体是酰胺化胃泌素的必备前体，与 在生理刺激下，胃泌素与胃泌素一起分泌。Gly扩展 胃泌素被证明是通过一个单独的受体刺激细胞生长的。装订 胃泌素/CCK-B受体及其激活的结构要求 并对G蛋白进行了研究。转录的几个关键组成部分 确定了胃泌素/CCK-B受体基因的调控。现在 提案旨在扩大这些研究的范围。以下具体目标将 被追捕。1)阐明胃泌素/CCK-B的结构成分 决定细胞生长和分泌的重要受体；2) 鉴定胃泌素/CCK-B受体基因的结构成分 在确定其表达和功能方面很重要；3)检查 Gly延伸胃泌素介导的与细胞生长相关的受体后事件； 4)进一步鉴定Gly延伸的胃泌素受体并克隆其 相应的cDNAs。

DESCRIPTION (Adapted from the applicant's abstract): This is a proposal to continue studies on the properties and function of the gastrin/CCK-B receptor and a putative receptor for Gly-extended gastrin (G-Gly). During the previous funding period, the PI and his collaborators have shown that the Gly-extended intermediate, an obligatory precursor of amidated gastrin, is stored with gastrin and secreted with it in response to physiological stimuli. Gly-extended gastrin was shown to stimulate cell growth via a separate receptor. The binding of the gastrin/CCK-B receptor and the structural requirements for activation of G proteins were also studied. Several key components of transcriptional regulation of the gastrin/CCK-B receptor gene were identified. The present proposal is designed to extend these studies. The following specific aims will be pursued. 1) elucidate the structural components of the gastrin/CCK-B receptor that are important in determining cell growth and secretion; 2) characterize the structural components of the gastrin/CCK-B receptor gene that are important in determining its expression and function; 3) examine the post-receptor events linked to cell growth mediated by Gly-extended gastrin; and 4) further characterize the receptor for Gly-extended gastrin and clone its corresponding cDNA.