Host signaling pathways targeted by a Yersinia effector

耶尔森氏菌效应子靶向的宿主信号通路

• 批准号: 6584504
• 负责人: CHRISTINE L MCDONALD
• 金额: $ 4.64万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584504
• 关键词: SDS polyacrylamide gel electrophoresis; X ray crystallography; Yersinia pestis disease; bacteria infection mechanism; biological signal transduction; enzyme activity; host organism interaction; immunoprecipitation; leucine; postdoctoral investigator; protein protein interaction; protein structure function; serine threonine protein kinase; tissue /cell culture; virulence

DESCRIPTION (provided by applicant): Yersinia pestis, the causative agent of plague, frequently results in fatal infections. Understanding the molecular mechanisms of bacterial pathogenesis has become increasingly important due to the recent concerns about bioterrorism and the development of measures to counteract these infectious agents. Yersinia injects effector proteins into host cells to inactivate the host immune response. One effector, YopM, is necessary for Yersinia virulence, but how this protein functions in host cells is unknown. The overall aim of this proposal is to identify the molecular mechanisms of how YopM contributes to the virulence of Yersinia. In this research proposal, protein kinase C-like 2 (PRK2) is identified as the first intracellular target of YopM. PRK2 is a serine/threonine kinase that has been implicated in regulation of apoptosis modulation of the actin cytoskeleton, and as a downstream effector of receptor tyrosine kinases. These studies of YopM will determine how the interaction of YopM with PRK2 alters PRK2 kinase activity, affects cellular signaling pathways, characterize the interaction of these proteins by biochemical and crystallographic approaches, as well as examine the conservation of these functions in structurally similar proteins from other bacteria.

描述（由申请人提供）：鼠疫耶尔森氏菌是鼠疫的病原体，经常导致致命的感染。 由于最近对生物恐怖主义的担忧以及对抗这些传染原的措施的发展，了解细菌发病机制的分子机制变得越来越重要。耶尔森氏菌将效应蛋白注入宿主细胞以使宿主免疫反应失活。 YopM 是耶尔森菌毒力所必需的一种效应蛋白，但这种蛋白在宿主细胞中如何发挥作用尚不清楚。该提案的总体目标是确定 YopM 如何促进耶尔森氏菌毒力的分子机制。在本研究提案中，蛋白激酶 C 样 2 (PRK2) 被确定为 YopM 的第一个细胞内靶标。 PRK2 是一种丝氨酸/苏氨酸激酶，与肌动蛋白细胞骨架的凋亡调节有关，并且是受体酪氨酸激酶的下游效应器。 YopM 的这些研究将确定 YopM 与 PRK2 的相互作用如何改变 PRK2 激酶活性、影响细胞信号传导途径、通过生化和晶体学方法表征这些蛋白质的相互作用，以及检查这些功能在来自其他结构相似的蛋白质中的保守性。细菌。