SIGNAL TRANSDUCTION BY A YEAST TWO COMPONENT REGULATOR

酵母二组分调节器的信号转导

• 批准号: 2447493
• 负责人: JAN S. FASSLER
• 金额: $ 23.17万
• 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/2447493
• 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：本提案的目标是确定酵母如何 “双成分”调节因子 Sln1p 控制必需酶的活性 转录因子Mcm1p。 Sln1p 被描述为 传感器-发射器负责渗透压的初始转导 通过 Hog1p MAP 激酶级联传递应激信号。 作者发现 此外，Sln1p 控制 Mcm1p 的活性：激活 sln1* 突变刺激 Mcm1p 依赖性报告基因 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：发现两条途径都依赖于 Sln1p 和磷继电器中间体 Ypd1p，但信号与 受体分子的身份。 Ssk1p 是受体分子 Hog1p 通路对 Mcm1p 的调节没有贡献，而最近 Fassler 博士的结果表明 Skn7p 可能是 Mcm1p 途径。 因此，下游成分的突变 Hog1p MAP 激酶级联对 Mcm1p 活性没有影响。 表型 sln1* 突变体的分析揭示了渗透敏感性，表明 Hog1p 和 Mcm1p 分支由 Sln1p 相互控制 磷酸化（磷酸化增加导致伴随的渗透压 由于 Hog1p 信号传导减少和 Mcm1p 信号增加而导致的敏感性 活动）。 作者打算通过以下方式继续进行分析： 并表征介导 Sln1p 对 Mcm1p 控制的因素； 表征 Sln1p 介导的 Mcm1p 信号传导的生物化学特征；和 表征响应 Sln1p 所需的 Mcm1p 区域 信号。