Phosphorylation and ubiquitination of immune sensory complexes in innate immune s

先天免疫中免疫感觉复合物的磷酸化和泛素化

• 批准号: 8840269
• 负责人: Libo Shan
• 金额: $ 24.32万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8840269
• 关键词: Animal Model; Animals; Arabidopsis; Architecture; BAK1 gene; Biochemical; Biological; Biological Assay; Cell Surface Receptors; Cell membrane; Cell physiology; Cells; Chitin; Communicable Diseases; Complex; Detection; EEF1A1 gene; Elongation Factor; Eukaryota; Event; Flagellin; Genetic; Genomics; Goals; Immune; Immune system; Infection; Knock-out; Ligand Binding; Lipopolysaccharides; MAP Kinase Modules; Mission; Modeling; Molecular; Natural Immunity; Nitric Oxide; Organism; Orthologous Gene; Pattern; Pattern recognition receptor; Peptidoglycan; Perception; Phosphorylation; Phosphotransferases; Physiological Processes; Plants; Prevention; Production; Reactive Oxygen Species; Receptor Activation; Receptor Signaling; Regulation; Research; Resources; Role; Sensory; Signal Transduction; Toll-like receptors; Transgenic Organisms; Ubiquitination; United States National Institutes of Health; Whole Organism; antimicrobial; base; insight; microbial; microorganism; novel; pathogen; pattern perception; receptor; ubiquitin-protein ligase

DESCRIPTION (provided by applicant): Plants and animals rely on immune sensory complexes to detect infection by recognizing evolutionarily conserved pathogen components. Plant immune senor FLS2, a structural and functional ortholog of mammalian Toll-like receptors (TLR), recognizes bacterial flagellin and initiates immune signaling by association with a receptor-like kinase BAK1. It remains unknown how FLS2/BAK1 receptor complex activates intracellular signaling cascades. We have identified two important phosphorylation substrates of BAK1 kinase. BIK1, an FLS2/BAK1-associated cytosolic kinase, is rapidly phosphorylated and released from FLS2/BAK1 receptor complex upon flagellin perception to propagate immune signaling. FCU, an E3 ubiquitin ligase, associates with FLS2 upon flagellin stimulation and ubiquitinates FLS2 receptor. BIK1 transphosphorylates BAK1/FLS2, which in turn enhances BAK1 phosphorylation on FCU. The objective of this application is to examine the role of BIK1 and FCU as convergent components in transducing innate immune signaling from receptor complexes to downstream intracellular events, and the biological significance of phosphorylation and ubiquitination in activating and regulating immune sensory complexes. Three specific aims are 1) Elucidate the role of receptor-associated kinase in innate immune signaling. 2) Determine the function of E3 ubiquitin ligase in innate immune signaling. 3) Characterize the ubiquitination of PAMP receptor complexes. Recent advance on the molecular architecture of nonself recognition has revealed remarkable conservation in the mechanisms of microbial perception and innate immune signaling in multicellular eukaryotes. Phosphorylation and ubiquitination are two key mechanisms in regulating many cellular and organismal processes, including innate immunity. The power of Arabidopsis genetics and genomics provides an excellent model to understand the functions of these two universal regulatory mechanisms at the whole organism level. Thus, the proposed research will provide new insight on signal transduction in general and contribute to the understanding of innate immune signaling and immune sensory complex function.

描述(申请人提供)：植物和动物依靠免疫感觉复合体，通过识别进化上保守的病原体成分来检测感染。植物免疫感受器Fls2是哺乳动物Toll样受体(TLR)的结构和功能同源物，它识别细菌鞭毛蛋白，并通过与受体样激酶BAK1结合来启动免疫信号。目前尚不清楚Fls2/BAK1受体复合体如何激活细胞内信号转导通路。我们已经确定了BAK1激酶的两个重要的磷酸化底物。BIK1是一种与Fls2/BAK1相关的胞浆激酶，在鞭毛蛋白作用下被迅速磷酸化并从Flas2/BAK1受体复合体中释放出来，以传播免疫信号。Fcu是一种E3泛素连接酶，在鞭毛蛋白刺激下与Fls2结合，泛素化Fls2受体。BIK1转磷酸化BAK1/Fls2，进而增强BAK1在FCU上的磷酸化。本应用的目的是研究BIK1和FCU作为聚合成分在将天然免疫信号从受体复合体传递到下游细胞内事件中的作用，以及磷酸化和泛素化在激活和调节免疫感觉复合体中的生物学意义。三个特定的目的是：1)阐明受体相关激酶在先天性免疫信号中的作用。2)确定E3泛素连接酶在先天免疫信号中的作用。3)研究PAMP受体复合体的泛素化。最近在非我识别的分子结构方面的进展揭示了多细胞真核生物的微生物感知和天然免疫信号机制的显着保守性。磷酸化和泛素化是调节许多细胞和生物过程的两个关键机制，包括先天免疫。拟南芥遗传学和基因组学的力量为在整个生物体水平上理解这两种普遍的调控机制的功能提供了一个很好的模型。因此，这项研究将为信号转导提供新的视角，并有助于理解先天免疫信号和免疫感觉复合体的功能。