UNDERSTANDING THE FIDELITY OF MAP KINASE SIGNALING

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 丝裂原活化蛋白激酶（Mitogen-activated protein kinase，MAPK）信号通路在真核细胞中起着重要的作用，作为信号转导子参与了许多生物学过程，包括生长、分化和应激反应。 在酵母中，交配，双渗透和高渗透压甘油（HOG）途径引起对不同刺激的特异性反应，但共享多个组件。 我们观察到，在通过HOG途径的信号传导过程中，交配和交配途径的MEK和MAPK在其活化残基上被磷酸化。 因此，MAPKs的下游必须存在机制，以确保交配和交配基因不转录响应渗透胁迫。 此外，我们发现这是一种新的机制，不同于用于防止诱导和交配途径之间的串扰的机制。 我们测试了在交配和表达特异性转录因子Ste 12和Tec 1被募集到其基因靶点之前或之后是否实现了特异性，并发现在没有Hog 1的情况下，Tec 1与表达特异性启动子结合的水平大幅增加。 这表明Hog 1通过阻止Tec 1与其靶启动子结合在抑制错误信号传导中起重要作用。 这些结果指出了真核细胞用于执行维持信号特异性的不可或缺的功能的新的调节模式。

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.