SOMATOSTATIN BIOSYNTHESIS AND SECRETION

生长抑素生物合成和分泌

• 批准号: 3234450
• 负责人: BERNARD A ROOS
• 金额: $ 10.1万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3234450
• 关键词: antiadrenergic agents; anticholinergic agent; calcitonin; electrofocusing; eukaryote; gel electrophoresis; hormone biosynthesis; hormone regulation /control mechanism; ion transport; neural information processing; nutrition related tag; organ culture; peptide hormone biosynthesis; peptide hormone metabolism; peptides; radioimmunoassay; radiotracer; secretion; somatostatin; tissue /cell culture; vitamin D

Somatostatin is a tetradecapeptide that can modulate a host of important neuroendocrine functions. We have established a permanent rat C-cell line that maintains very high levels of somatostatin production. We have used this thyroid C-cell line to identify and characterize somatostatin's 92-amino-acid biosynthetic precursor, prosomatostatin. The structures of somatostatin and other peptides derived from prosomatostatin's carboxyl-terminal 28 residues are proven. Those putatively derived from the amino-terminal 64 residues of prosomatostatin are not proven. We propose to ascertain the structure of biosynthetic intermediates and secretory peptides generated as a consequence of prosomatostatin processing, particularly processing within the amino-terminal two thirds of the precursor and to identify factors that regulate the synthesis and cleavage/degradation of prosomatostatin and its derived intermediate and final products. To achieve these aims cellular and secretory peptides that cross-react with antibodies directed at specific sequences in the amino-terminal 64-residue portion of prosomatostatin will be purified from the cell cultures and their structures ascertained. Then pulse-chase studies will be conducted in the somatostatin-producing cell line to establish the origin of these peptides from prosomatostatin and derived biosynthetic intermediates. Some studies will be directed at identifying factors that regulate this biosynthetic process and comparing regulatory effects on the various prosomatostatin-derived secretory products characterized by our structural analyses. Such work is a critical step toward the long-term objectives of this research program which include: a) elucidation of the somatostatin precursor and its co- and post-translational processing in normal and neoplastic tissues; b) the determination of the factors that regulate the biosynthesis and secretion of prosomatostatin-derived peptides and elucidation of the mechanisms underlying that regulation; and c) understanding the biological importance of the multiple peptides that result from somatostatin gene expression.

生长抑素是一种十四肽，可以调节许多重要的 神经内分泌功能 我们已经建立了一个永久的大鼠C细胞系 维持着高水平的生长抑素分泌。 我们已经使用 这种甲状腺C细胞系，以确定和表征生长抑素的 92-氨基酸生物合成前体，促生长素抑制素。 的结构 促生长素抑制素和衍生自促生长素抑制素原的其它肽 羧基末端28个残基被证明。 这些脓液来源于 促生长素抑制素的氨基末端64个残基未被证实。 我们 建议确定生物合成中间体的结构， 促生长素抑制素原产生的分泌肽 加工，特别是在氨基末端三分之二内的加工， 前体，并确定调节合成的因素， 促生长素抑制素原及其衍生中间体的裂解/降解， 最终产品。 为了实现这些目标，细胞和分泌肽， 与针对特定序列的抗体发生交叉反应， 将生长抑素原的氨基末端64个残基部分从 细胞培养物及其结构已确定。 然后脉冲追踪 将在生长抑素产生细胞系中进行研究， 建立这些肽的来源，从促生长素抑制素和衍生 生物合成中间体 一些研究将致力于确定 调节这种生物合成过程的因素， 对各种促生长素抑制素衍生分泌产物的影响 通过我们的结构分析。 这项工作是关键的一步 实现本研究计划的长期目标，包括：a） 生长激素抑制素前体及其共-和 正常和肿瘤组织中的翻译后加工; B） 确定调节生物合成和分泌的因子 促生长素抑制素衍生肽的合成及其机制的阐明 （c）理解生物学的重要性; 由生长抑素基因表达产生的多种肽。