Characterization of the S. Pombe cAMP Pathway

粟酒裂殖酵母 cAMP 途径的表征

• 批准号: 6732673
• 负责人: CHARLES S. HOFFMAN
• 金额: $ 30.6万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732673
• 关键词: G protein; Schizosaccharomyces pombe; adenylate cyclase; biological signal transduction; cyclic AMP; enzyme activity; fungal genetics; gene mutation; glucose metabolism; glucose receptor; molecular cloning; receptor coupling

DESCRIPTION: (Adapted from the Investigator's abstract): One way cells respond to their environment is by creating internal signals that regulate gene expression. Human and yeast cells employ homologous signaling pathways to control cell growth, stress response, metabolic pathways and differentiation. Therefore, the relatively simple and genetically pliable budding and fission yeasts are valuable model organisms providing important insights to mechanisms of signal transduction in mammalian cells. My laboratory studies the glucose/cAMP signal pathway that is central to the transcriptional regulation of the fission yeast fbpl gene. Environmental glucose triggers the activation of adenylate cyclase, and the resulting cAMP signal activates protein kinase A to repress fbpI transcription. Many, but not all, of the genes we have identified in this pathway in fission yeast encode proteins whose human homologues carry out similar functions in cAMP signaling. Therefore this model system has the potential both to advance our structural understanding of conserved signaling mechanisms and to lead to novel discoveries. In addition, the catalytic domain of fission yeast adenylate cyclase enzyme closely resembles those of several pathogenic organisms including the human pathogens Trypanosoma brucei and Candida albicans. While the cAMP pathway appears to be important to growth and differentiation of these organisms, nothing is known about the regulation of their adenylate cyclase enzymes. Therefore, our studies may suggest potential targets for inhibiting the growth or invasiveness of these pathogens. We propose to continue our work on adenylate cyclase activation by conducting genetic, molecular and biochemical studies of the fission yeast glucose/cAMP pathway.

描述：（从研究者的摘要中进行了改编）：单元单元响应 对他们的环境是通过创建调节基因的内部信号 表达。人类和酵母细胞采用同源信号通路 控制细胞生长，应力反应，代谢途径和分化。 因此，相对简单且遗传上柔韧的萌芽和裂变 酵母是有价值的模型生物，为机制提供了重要的见解 哺乳动物细胞中信号转导的。我的实验室研究 葡萄糖/cAMP信号途径是转录调节的中心 裂变酵母FBPL基因的。环境葡萄糖会触发激活 腺苷酸环化酶的且所得的CAMP信号激活蛋白激酶A 抑制FBPI转录。我们拥有的许多基因，但不是全部 在裂变酵母中鉴定在该途径中的人类的蛋白质 同源物在cAMP信号传导中执行类似的功能。因此，这个模型 系统有潜力既可以提高我们对 保守的信号机制并导致新发现。此外， 裂变酵母腺苷酸环化酶的催化结构域紧密 类似于包括人类病原体在内的几种病原生物 布鲁氏锥虫和白色念珠菌。而露营路似乎是 对于这些生物的生长和差异很重要，没有什么已知的 关于其腺苷酸环化酶酶的调节。因此，我们的研究 可能建议抑制抑制生长或侵入性的潜在目标 这些病原体。我们建议继续我们在腺苷酸环化酶上的工作 通过进行遗传，分子和生化研究的激活 裂变酵母葡萄糖/营地。