G PROTEIN-MEDIATED NUTRITIONAL SIGNALING IN YEAST

酵母中 G 蛋白介导的营养信号传导

• 批准号: 6343086
• 负责人: Jeanne P. Hirsch
• 金额: $ 24.19万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6343086
• 关键词: G protein; biological signal transduction; cell growth regulation; fungal genetics; growth media; guanine nucleotide binding protein; guanosine triphosphate; microorganism growth; nutrient requirement; nutrition related tag; pheromone; plant physiology; receptor binding; receptor coupling; yeasts

Cell growth is regulated by signal transduction pathways that respond to extracellular stimuli. In yeast, the signal that promotes growth is thought to be the availability of nutrients. Nutritional signaling involves the activation of Ras proteins and adenylyl cyclase through a process that is not well understood. Results presented in this proposal demonstrate that nutritional signaling in yeast also involves the activation of a G protein alpha-subunit by a G protein-coupled receptor. Several observations suggest that this pathway is activated in response to nitrogen starvation. For example, strains lacking the receptor or the G protein are defective for pseudohyphal growth, a developmental switch that is induced by nitrogen starvation. The long-term objective of this project is a description of the mechanisms employed by the G protein-mediated pathway to signal in response to nutritional conditions. Classical genetics and protein biochemistry will be used to elucidate the roles of genes and their encoded proteins in this process. The aims of this project are to characterize and identify the ligand for a newly described G protein-coupled receptor and to determine when the receptor is physiologically active. The first specific aim will investigate the conditions under which the Gpr1p receptor is bound to its ligand. These studies will be performed by coupling the Gpr1p receptor to the pheromone response pathway and using a well-established reporter construct that detects activation of the pathway. The second specific aim will employ the Gpr1p reporter system to characterize and identify the Gpr1p ligand. Identification of such a ligand would be one of the first examples of a receptor-binding molecule that activates a nutritional signaling pathway in a eukaryotic organism. The final specific aim will characterize the regulation of Gpr1p receptor expression and stability. Investigation of this novel signaling system will contribute to an understanding of nutritional signaling in eukaryotes, an area in which many important questions have not yet been addressed. Significant progress in elucidating signal transduction mechanisms has been made in organisms in which sophisticated genetic manipulations can easily be performed. A complete understanding of growth control in yeast is likely to provide insight into growth control in mammals, which is also regulated by signaling through G proteins and Ras. Such information is essential for understanding the process of carcinogenesis, in which cells escape this regulation and exhibit uncontrolled growth.

细胞生长受到对细胞外刺激反应的信号转导途径的调节。 在酵母中，促进生长的信号被认为是营养的可用性。营养信号传导涉及RAS蛋白和腺苷酸环化酶的激活，该过程尚不清楚。该提案中提出的结果表明，酵母中的营养信号传导还涉及G蛋白偶联受体激活G蛋白α-亚基。 几种观察结果表明，该途径是响应氮饥饿而激活的。 例如，缺乏受体或G蛋白的菌株对于假氢生长而言是有缺陷的，这是一种由氮饥饿诱导的发育开关。该项目的长期目的是描述G蛋白介导的途径对营养条件的信号所采用的机制。 经典的遗传学和蛋白质生物化学将用于阐明基因及其编码蛋白在此过程中的作用。该项目的目的是表征和识别新描述的G蛋白偶联受体的配体，并确定受体何时生理活性。 第一个具体目的将研究GPR1P受体与配体结合的条件。 这些研究将通过将GPR1P受体耦合到信息素响应途径，并使用良好的记者构建体来进行这些研究。 第二个特定目的将采用GPR1P报告程序系统来表征和识别GPR1P配体。 这种配体的识别将是受体结合分子的第一个例子之一，该分子激活真核生物中营养信号通路。 最终的特定目的将表征GPR1P受体表达和稳定性的调节。对这种新型信号系统的研究将有助于理解真核生物中的营养信号传导，在该领域中尚未解决许多重要问题。在阐明信号转导机制方面取得了重大进展，在生物体中可以轻松地进行复杂的遗传操作。 对酵母中生长控制的完全了解可能会洞悉哺乳动物的生长控制，这也通过通过G蛋白和RAS信号来调节。 这种信息对于理解癌变过程至关重要，其中细胞逃脱了这种调节并表现出不受控制的生长。