OSMOREGULATORY SIGNAL TRANSDUCTION IN YEAST

酵母中的渗透调节信号转导

• 批准号: 6138590
• 负责人: Haruo Saito
• 金额: $ 24.87万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138590
• 关键词: biological signal transduction; cell osmotic pressure; gene mutation; mitogen activated protein kinase; phosphorylation; yeasts

DESCRIPTION: The long-term objective of this application is to understand in molecular terms how intracellular signal transduction is mediated by protein phosphorylation and dephosphorylation. This proposal intends to study the genetic and biochemical bases of osmoregulatory signal transduction in budding yeast. The yeast response to high external osmolarity is governed by two independent osmosensors, SLN1 and SHO1. Although these osmosensors are structurally distinct, they ultimately regulate the same downstream element, the HOG1 MAP kinase. Yeast is an ideal model system to study the general principles governing intracellular signal transduction, not only because it is genetically tractable, but also because its signaling pathways have many features in common with human cells. SLN1 and SHO1 are the only eukaryotic models currently available for the mammalian osmosensors, which have not been molecularly identified. Mammalian osmoregulation is important for the maintenance of homeostasis as well as for kidney function. The regulatory mechanism of a MAPK cascade is particularly important to mammalian oncogenesis, because many oncogenes exert their effects through hyperactivation of MAP kinases. The specific aims of this proposal are: 1) Studies on the SLN1 osmosensing mechanism, and the regulation of the SLN1-YPD1-SSK1 phosphorelay. SLN1 mutants that are defective in signal sensing or transmission, and their intragenic suppressor mutants, will be isolated and characterized. Regulators of the SLN1-YPD1-SSK1 phsophorelay, such as a histidine phosphatase or an aspartate phosphatase, will be identified and studied. Studies on the SSK2/SSK22 ativation mechanism by SSK1. The domains that are essential for the interaction of SSK1 and the SSK2/SSK22 MAPKKKs will be identified. Three specific SSK2 activation mechanisms will then be addressed: dimerization of SSK2; involvement of an SSK2 autoinhibitory site; and phosphorylation of SSK2 either by an autophosphorylation mechanism or by another protein kinase. 3) Studies on the regulation of the STE11 MAPKKK and the PBS2 MAPKK by the SHO1 osmosensor. Additional components on the SHO1 branch of the yeast osmoregulatory signal pathway will be identified, and the mechanism that determines the specificity of the PBS2 and STE11 kinases will be investigated. Finally, the SHO1 osmosensing mechanism will be genetically analyzed.

描述：本应用程序的长期目标是了解 用分子术语，细胞内信号转导如何介导 蛋白质磷酸化和去磷酸化。 该提议打算 研究渗透测量信号的遗传和生化基础 发芽酵母的转导。 酵母对高外部的反应 渗透性由两个独立的渗透传感器SLN1和SHO1支配。 尽管这些Osmossenor在结构上是不同的，但它们最终 调节相同的下游元素，HOG1 MAP激酶。 酵母是一个 理想的模型系统，用于研究有关细胞内的一般原则 信号转导，不仅是因为它是遗传处理的，而且还因为 因为它的信号通路与人类具有许多共同点 细胞。 SLN1和SHO1是目前可用于的唯一可用于 哺乳动物的渗透传感器，尚未分子鉴定。 哺乳动物的渗透调节对于维持体内平衡很重要 以及肾功能。 MAPK级联的调节机制是 对于哺乳动物的肿瘤发生尤其重要，因为许多肿瘤基因 通过MAP激酶的过度激活发挥其作用。 具体 该提案的目的是：1）有关SLN1渗透压机制的研究， 以及SLN1-ippd1-SSK1磷质的调节。 SLN1突变体 在信号传感或传输方面有缺陷，其内部性 抑制突变体将被隔离和表征。 监管机构 SLN1-ippd1-SSK1 pHSophoreLay，例如组氨酸磷酸酶或天冬氨酸 磷酸酶将被鉴定和研究。 SSK2/SSK22的研究 SSK1的生气机制。 对于 将确定SSK1和SSK2/SSK22 MAPKKK的相互作用。 三 然后将解决特定的SSK2激活机制： SSK2; SSK2自抑制部位的参与；和磷酸化 SSK2通过自磷酸化机制或另一种蛋白质 激酶。 3）研究Ste11 mapkk和PBS2 MAPKK的调节研究 由Sho1 Osmosensor。 SHO1分支上的其他组件 将确定酵母Osmoregulatoration信号途径，并进行机制 决定PBS2和Ste11激酶的特异性将是 调查。 最后，SHO1渗透压机制将是基因的 分析。