UNDERSTANDING THE FIDELITY OF MAP KINASE SIGNALING

了解 MAP 激酶信号转导的保真度

• 批准号: 8171295
• 负责人: Hiten D Madhani
• 金额: $ 0.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171295
• 关键词: Binding; Biological Process; Computer Retrieval of Information on Scientific Projects Database; Differentiation and Growth; Ensure; Eukaryotic Cell; Funding; Gene Targeting; Genes; Glycerol; Grant; Institution; MEKs; Maps; Mitogen-Activated Protein Kinases; Osmolar Concentration; Partner in relationship; Pathway interactions; Phosphotransferases; Play; Recruitment Activity; Regulation; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Specificity; Stimulus; Stress; Testing; Transducers; United States National Institutes of Health; Yeasts; novel; prevent; promoter; response; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mitogen-activated protein kinase (MAPK) signaling cascades play a fundamental role in eukaryotic cells, acting as signal transducers involved in many biological processes including growth, differentiation and response to stress. In yeast, the mating, filamentation, and high osmolarity glycerol (HOG) pathways elicit specific responses to distinct stimuli, yet share multiple components. We observed that both the MEK and the MAPKs of the mating and filamentation pathways are phosphorylated on their activating residues during signaling through the HOG pathway. Therefore, mechanisms must exist downstream of the MAPKs to ensure that mating and filamentation genes are not transcribed in response to osmotic stress. In addition, we found that this is a novel mechanism, distinct from the mechanisms used to prevent cross-talk between the filamentation and mating pathways. We tested whether specificity is achieved before or after the mating and filamentation specific transcription factors, Ste12 and Tec1, are recruited to their gene targets, and found that in the absence of Hog1 there is a large increase in the levels of Tec1 binding to filamentation specific promoters. This indicates that Hog1 plays an essential role in inhibiting erroneous signaling by preventing Tec1 from binding to its target promoters. These results point to new modes of regulation used by eukaryotic cells to perform the indispensable function of maintaining signaling specificity.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 丝裂原激活蛋白激酶 (MAPK) 信号级联在真核细胞中发挥着重要作用，作为参与许多生物过程（包括生长、分化和应激反应）的信号转导器。 在酵母中，交配、丝化和高渗透甘油 (HOG) 途径会引发对不同刺激的特定反应，但共享多种成分。 我们观察到，交配和丝化途径的 MEK 和 MAPK 在通过 HOG 途径进行信号传导期间，其激活残基均被磷酸化。 因此，MAPK 下游必须存在机制，以确保交配和丝状基因不会因渗透胁迫而转录。 此外，我们发现这是一种新颖的机制，不同于用于防止丝状化和交配途径之间串扰的机制。 我们测试了在交配和丝状化特异性转录因子 Ste12 和 Tec1 被招募到其基因靶标之前或之后是否实现了特异性，并发现在缺乏 Hog1 的情况下，Tec1 与丝状化特异性启动子的结合水平大幅增加。 这表明 Hog1 通过阻止 Tec1 与其靶启动子结合而在抑制错误信号传导中发挥重要作用。 这些结果指出真核细胞使用新的调节模式来执行维持信号特异性的不可或缺的功能。