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: 6891958
• 负责人: CHRISTINE L MCDONALD
• 金额: $ 2.9万
• 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 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6891958
• 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）：鼠疫的致病药物耶尔森尼亚·佩斯蒂斯（Yersinia Pestis）经常导致致命感染。 由于最近对生物恐怖主义的关注以及抵消这些感染因子的措施的发展，了解细菌发病机理的分子机制已变得越来越重要。 Yersinia将效应蛋白注射到宿主细胞中，以使宿主免疫反应失活。一种效应子YOPM是耶尔森氏症毒力所必需的，但是该蛋白在宿主细胞中的作用尚不清楚。该提案的总体目的是确定YOPM如何促进Yersinia的分子机制。在这项研究建议中，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，与调节肌动蛋白细胞骨架的凋亡调节有关，作为受体酪氨酸激酶的下游效应子。 这些对YOPM的研究将决定YOPM与PRK2的相互作用如何改变PRK2激酶活性，影响细胞信号通路，表征这些蛋白质通过生化和晶体学方法的相互作用，并检查这些功能在与其他细菌的结构相似蛋白质中的保护。