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: 8463568
• 负责人: Libo Shan
• 金额: $ 23.47万
• 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 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8463568
• 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（由申请人提供）：植物和动物依靠免疫感觉复合物通过识别进化上保守的病原体成分​​来检测感染。植物免疫传感器 FLS2 是哺乳动物 Toll 样受体 (TLR) 的结构和功能直系同源物，可识别细菌鞭毛蛋白并通过与受体样激酶 BAK1 结合启动免疫信号传导。 FLS2/BAK1 受体复合物如何激活细胞内信号级联仍不清楚。我们已经鉴定了 BAK1 激酶的两个重要的磷酸化底物。 BIK1 是一种 FLS2/BAK1 相关胞质激酶，在鞭毛蛋白感知后迅速磷酸化并从 FLS2/BAK1 受体复合物中释放，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 结合并泛素化 FLS2 受体。 BIK1 转磷酸化 BAK1/FLS2，进而增强 FCU 上的 BAK1 磷酸化。本申请的目的是检查 BIK1 和 FCU 作为汇聚成分在将先天免疫信号从受体复合物转导至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物中的生物学意义。三个具体目标是 1) 阐明受体相关激酶在先天免疫信号传导中的作用。 2) 确定E3泛素连接酶在先天免疫信号传导中的功能。 3) 表征 PAMP 受体复合物的泛素化。非自我识别分子结构的最新进展揭示了多细胞真核生物中微生物感知和先天免疫信号传导机制的显着保守性。磷酸化和泛素化是调节许多细胞和生物过程（包括先天免疫）的两个关键机制。拟南芥遗传学和基因组学的力量提供了一个很好的模型来理解这两种通用调节机制在整个生物体水平上的功能。因此，拟议的研究将为信号转导提供新的见解，并有助于理解先天免疫信号和免疫感觉复合体功能。