Phosphorylation and ubiquitination of immune sensory complexes in innate immune signaling

先天免疫信号中免疫感觉复合物的磷酸化和泛素化

• 批准号: 10065506
• 负责人: Libo Shan
• 金额: $ 26.71万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 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 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10065506
• 关键词: Amino Acids; Animals; Arabidopsis; Architecture; Attenuated; BAK1 gene; Biochemical; Biological Process; Biological Response Modifiers; Cell Surface Receptors; Cell membrane; Cell physiology; Cells; Communicable Diseases; Complex; Data; Detection; Diacylglycerol Kinase; Eukaryota; Event; Exposure to; Flagellin; Foundations; Gene Expression; Generations; Genetic; Genomics; Goals; Heterodimerization; Immune; Immune signaling; Immune system; Immunity; Infection; Knock-out; Ligands; Light; MAP Kinase Modules; Mediating; Microbe; Mission; Modeling; Molecular; Monoubiquitination; Natural Immunity; Orthologous Gene; Pattern; Pattern recognition receptor; Peptides; Perception; Phosphatidic Acid; Phosphorylation; Phosphotransferases; Physiological Processes; Plants; Polyubiquitination; Production; Reactive Oxygen Species; Receptor Signaling; Regulation; Research; Resources; Sensory; Signal Transduction; Structure; System; Testing; Toll-like receptors; Transgenic Organisms; Ubiquitination; United States National Institutes of Health; antimicrobial; base; dimer; extracellular signal-regulated kinase 4; gene function; microbial; microorganism; novel; pathogen; pattern perception; prevent; receptor; trafficking; ubiquitin-protein ligase

Phosphorylation and ubiquitination of immune sensory complexes in innate immune signaling Project Summary Plants and animals rely on pattern-recognition receptors (PRRs) to detect infection by recognizing microbe-associated molecular patterns (MAMPs). FLS2, a structural and functional ortholog of mammalian Toll-like receptors (TLRs) in plants, recognizes bacterial flagellin and initiates immune signaling by dimerizing with a co-receptor BAK1. With the previous NIH support, we have identified a plasma membrane-tethered receptor-like cytoplasmic kinase (RLCK) BIK1 as a convergent immune regulator by association with multiple PRR complexes. MAMP perception induces rapid BIK1 phosphorylation by BAK1, and subsequent release from PRR complexes to transduce diverse immune signaling. It remains unknown how PRR-associated BIK1 is activated and then bifurcates intracellular PRR signaling. Our preliminary data indicate that MAMP perception triggers rapid mono-ubiquitination of BIK1 and related RLCKs. A RING-type E3 ubiquitin ligase BMU1, that is phosphorylated by BIK1, mediates MAMP-induced BIK1 ubiquitination. BIK1 interacts and phosphorylates a diacylglycerol kinase DGK5 that regulates MAMP-induced phosphatidic acid (PA) production. Three over-arching aims are proposed to test a central hypothesis that mono-ubiquitination of BIK1 by BMU1 triggers release of BIK1 from PRR complexes, and subsequent endosomal trafficking and relaying intracellular signaling events, including activation of DGK5 for PA production. Three specific aims are 1. Ubiquitination of BIK1 by BIK1-phosphorylated BMU1 in plant immunity; 2. Ligand-induced BIK1 mono-ubiquitination in endosomal trafficking and plant immunity; 3. Dual phosphorylation of DGK5 by PRR-activated BIK1 and MAP kinase 4 in plant immunity. 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 diverse cellular and organismal processes. Our project on pathogen- induced sequential and intertwined phosphorylation and ubiquitination orchestrating PRR complex activation and signal transduction in plant immunity will generate conceptual advance in understanding the biological functions of these two universal regulatory mechanisms at the whole organismal level. The proposed research will also contribute to the general understanding of innate immune signaling and immune sensory complex function.

先天免疫信号传导中免疫感觉复合物的磷酸化和泛素化 项目摘要 植物和动物依赖于模式识别受体（PRRs）通过识别微生物相关蛋白来检测感染。 分子模式（MAMPs）。FLS 2是植物中哺乳动物Toll样受体（TLR）的结构和功能直系同源物， 识别细菌鞭毛蛋白并通过与共受体BAK 1二聚化启动免疫信号传导。与前一 在NIH的支持下，我们已经确定了质膜栓系受体样胞质激酶（RLCK）BIK 1作为一种细胞因子。 聚合免疫调节剂与多个PRR复合物。MAMP感知诱导快速BIK 1 通过BAK 1的磷酸化，以及随后从PRR复合物中释放，以促进多样化的免疫信号传导。它仍然是 目前尚不清楚PRR相关的BIK 1是如何被激活的，然后分叉细胞内PRR信号传导。我们的初步数据 表明MAMP感知触发BIK 1和相关RLCK的快速单泛素化。一种RING型E3泛素 连接酶BMU 1被BIK 1磷酸化，介导MAMP诱导的BIK 1泛素化。BIK 1相互作用， 磷酸化调节MAMP诱导的磷脂酸（PA）产生的二酰基甘油激酶DGK 5。三 过度的目的是为了检验一个中心假设，即BMU 1对BIK 1的单泛素化触发了BMU 1的释放。 来自PRR复合物的BIK 1，以及随后的内体运输和中继细胞内信号传导事件，包括 DGK 5的活化用于PA生产。 三个具体目标是 1.植物免疫中BIK 1-磷酸化BMU 1对BIK 1的泛素化作用 2.配体诱导的BIK 1单泛素化与内体运输和植物免疫 3.在植物免疫中通过PRR-activated BIK 1和MAP激酶4双重磷酸化DGK 5。 非自我识别的分子结构的最新进展揭示了在非自我识别中的显著保守性。 多细胞真核生物中微生物感知和先天免疫信号传导的机制。磷酸化和 泛素化是调节多种细胞和生物体过程的两种关键机制。我们的病原体项目- 诱导顺序和交织的磷酸化和泛素化协调PRR复合物激活和信号传导 植物免疫中的转导将在理解这两种蛋白的生物学功能方面产生概念性的进展。 在整个生物体水平上的普遍调节机制。这项研究也将有助于促进 理解先天免疫信号传导和免疫感觉复合体功能。