SIGNAL TRANSDUCTION BY A YEAST TWO COMPONENT REGULATOR

酵母二组分调节器的信号转导

• 批准号: 6138592
• 负责人: JAN S. FASSLER
• 金额: $ 24.03万
• 依托单位: UNIVERSITY OF IOWA
• 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/6138592
• 关键词: binding proteins; biological signal transduction; cell osmotic pressure; fungal genetics; gene mutation; protein structure function; transcription factor; yeasts

DESCRIPTION: The goal of this proposal is to determine how the yeast "two-component" regulator, Sln1p, controls the activity of the essential transcription factor Mcm1p. Sln1p has been characterized as the sensor-transmitter responsible for initial transduction of the osmotic stress signal through the Hog1p MAP kinase cascade. The authors have found that, additionally, Sln1p controls the activity of Mcm1p: activated sln1* mutations stimulate expression of the Mcm1p dependent reporter gene P-lacZ. Furthermore, regulation of Hog1p and Mcm1p define a branch point in the regulation conferred by Sln1p: both pathways were found to rely on Sln1p and the phosphorelay intermediate Ypd1p, but the signal diverges with the identity of the receiver molecule. Ssk1p is the receiver molecule for the Hog1p pathway and does not contribute to regulation of Mcm1p, whereas recent results from Dr. Fassler suggest that Skn7p is the likely receiver for the Mcm1p pathway. Accordingly, mutations in the downstream components of the Hog1p MAP kinase cascade have no effect on Mcm1p activity. Phenotypic analysis of the sln1* mutants reveals osmotic sensitivity indicating that the Hog1p and Mcm1p branches are reciprocally controlled by Sln1p phoshphorylation (increased phosphorylation results in concomitant osmotic sensitivity due to decreased signaling of Hog1p and increased Mcm1p activity). The authors intend to continue their analyses by: identifying and characterizing the factors mediating Sln1p control of Mcm1p; characterizing the biochemistry of Sln1p mediated signaling to Mcm1p; and characterizing the regions of Mcm1p required for response to the Sln1p signal.

描述：该提议的目的是确定酵母如何 “两个组件”调节器SLN1P控制着必需的活动 转录因子MCM1P。 SLN1P已被描述为 传感器发射器负责初始转移的渗透率 通过HOG1P MAP激酶级联反应的应力信号。 作者发现 另外，SLN1P控制了MCM1P的活性：活化的SLN1* 突变刺激MCM1P依赖性记者基因P-LacZ的表达。 此外，HOG1P和MCM1P的调节定义了一个分支点 SLN1P赋予的调节：发现两种途径依赖于SLN1P 和磷的中间YPD1P，但信号与 接收器分子的身份。 SSK1P是接收器分子 HOG1P途径，不促进MCM1P的调节 Fassler博士的结果表明，SKN7P可能是 MCM1P途径。 因此，在下游组成部分中的突变 HOG1P MAP激酶级联对MCM1P活性没有影响。 表型 SLN1*突变体的分析显示渗透敏感性表明 HOG1P和MCM1P分支由SLN1P相互控制 phoshphylation（磷酸化增加导致渗透性 由于HOG1P的信号降低和MCM1P的提高而引起的灵敏度 活动）。 作者打算通过以下方式继续进行分析 并表征介导MCM1P的SLN1P控制的因素； 表征了SLN1P介导的信号传导对MCM1P的生物化学；和 表征响应SLN1P所需的MCM1P区域 信号。