Characterization of the S. Pombe cAMP Pathway

描述：(改编自《调查者摘要》)：细胞的一种反应方式 是通过产生内部信号来调节基因 表情。人类和酵母细胞使用同源信号通路来 控制细胞生长、应激反应、代谢途径和分化。 因此，相对简单和遗传上柔韧的萌发和分裂 酵母菌是有价值的模式生物，为机制提供了重要的见解 哺乳动物细胞中信号转导的研究。我的实验室研究的是 转录调控中心的葡萄糖/cAMP信号通路 裂解酵母fbpl基因。环境中的葡萄糖触发了这种激活 腺苷环化酶的活性，由此产生的cAMP信号激活蛋白激酶A 以抑制FBPI转录。我们拥有的许多基因，但不是全部 在这一途径中鉴定的裂变酵母编码的蛋白质，其人 同系物在cAMP信号中执行类似的功能。因此，该模型 系统有可能促进我们对 保守的信号机制，并导致新的发现。此外, 裂解酵母腺苷酸环化酶的催化结构域紧密相关 与包括人类病原体在内的几种病原体相似 布鲁氏锥虫和白色念珠菌。虽然cAMP路径似乎是 对这些生物的生长和分化很重要，但目前尚不清楚 关于它们的腺苷环化酶的调节。因此，我们的研究 可能会提出潜在的目标，以抑制生长或侵袭性 这些病原体。我们建议继续我们对腺苷酸环化酶的研究 通过进行遗传、分子和生化研究来激活 裂解酵母葡萄糖/cAMP途径。

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.