CONTROL OF SIGMA B ACTIVITY IN B SUBTILIS

描述（改编自研究者摘要）：B。枯草杆菌σ-B 蛋白质参与应激反应的转录激活 调节子 在没有环境压力的情况下，sigma-B被保持在一个 具有反σ（RsbW）的非活性络合物。 未知的压力信号会导致 第二种调节蛋白RsbT磷酸化并磷酸化自身的蛋白质， 抑制剂RsbS。 活性RsbT指导磷酸酶RsbU， 去磷酸化另一个调节因子RsbV。 去磷酸化的RsbV可以 与RsbW结合，导致sigma-B释放，使sigma处于活性状态 作为转录因子。 该系统由第二磷酸酶重置， RsbX，它去磷酸化并重新激活RsbS，这样它就可以再次 抑制RsbT。 RsbT的抑制导致RsbV的磷酸化， 阻止与RsbW的交互，以便RsbW再次可用于 将sigma-B捕获在非活性复合物中。 该提案旨在确定如何 不同的压力可以与sigma-B的调节器通信， 其活动。 由于RsbX的缺失而导致的高sigma-B活性是有毒的 这允许抑制突变的分离，并且 识别参与该途径的基因。 RsbT和RsbX是 被认为是环境信号最有可能的直接目标; 这将通过详细的突变分析进行测试。 生物化学分析 将被用来监测体内磷酸化的RbsS，这是建议 是sigma-B激活级联反应的关键步骤 相互作用的蛋白质 与Rsb蛋白质将寻求通过生化分析和使用酵母 双杂交系统 由于在致病性疾病中发现了sigma-B同源物， 细菌，分析控制应激反应可能提供信息 关于对宿主的适应和传染性。

DESCRIPTION (adapted from investigator's abstract): The B. subtilis sigma-B protein is involved in activation of transcription of a stress response regulon. In the absence of environmental stress, sigma-B is held in an inactive complex with an anti-sigma (RsbW). Unknown stress signals cause a second regulatory protein, RsbT, to phosphorylate and inactivate its own inhibitor, RsbS. Active RsbT directs a phosphatase, RsbU, to dephosphorylate another regulator, RsbV. Dephosphorylated RsbV can then bind to RsbW, causing release from sigma-B, allowing the sigma to be active as a transcription factor. The system is reset by a second phosphatase, RsbX, which dephosphorylates and reactivates RsbS, so that it can again inhibit RsbT. Inhibition of RsbT results in phosphorylation of RsbV, preventing interaction with RsbW, so that RsbW is once again available to trap sigma-B in an inactive complex. The proposal seeks to determine how diverse stresses can communicate with the regulators of sigma-B to control its activity. High sigma-B activity, resulting from loss of RsbX, is toxic to the cell; this permits isolation of suppressor mutations, and identification of genes involved in this pathway. RsbT and RsbX are postulated to be the most likely direct targets of environmental signals; this will be tested by detailed mutational analysis. Biochemical analyses will be used to monitor in vivo phosphorylation of RbsS, which is proposed to be a key step in the sigma-B activation cascade. Proteins which interact with Rsb proteins will be sought by biochemical analyses and using the yeast dihybrid system. Since sigma-B homologs have been discovered in pathogenic bacteria, analysis of control of the stress response may provide information about adaptation to the host and infectivity.