卡氏肺孢子虫中的信息素信号转导-猫眼课题宝

卡氏肺孢子虫中的信息素信号转导

批准号：

7576182

负责人：

CHARLES FRANCIS THOMAS

金额：

$27.44万

依托单位：

MAYO CLINIC ROCHESTER

依托单位国家：

美国

项目类别：

财政年份：

2002

资助国家：

美国

项目状态：

已结题

起止时间：

2002-03-01 至 2010-11-28

来源：

https://reporter.nih.gov/project-details/7576182

关键词：

Acquired Immunodeficiency Syndrome Adrenal Cortex Hormones Autoradiography Binding Binding Sites Biochemical Biology Cell Cycle Chimeric Proteins Complement Cyst Databases Epithelium Figs - dietary Gel Gene Expression Genes Infection Investigation Life Cycle Stages Ligands Lung MEKs Mass Spectrum Analysis Mating Types Mitogen-Activated Protein Kinases Organism Orthologous Gene Pathogenicity Pathway interactions Patients Pheromone Pheromone Receptors Phosphorylation Phosphorylation Site Phosphotransferases Pneumocystis Pneumocystis carinii Pneumocystis carinii Pneumonia Pneumonia Population Procedures Process Proliferating Promoter Regions Protein Analysis Proteins Proteomics Radioactive Reaction Receptor Signaling Recombinants Regulation Reporter Genes Research Personnel Response Elements Reverse Transcriptase Polymerase Chain Reaction Role Saccharomyces cerevisiae Signal Pathway Signal Transduction Site Site-Directed Mutagenesis Sorting - Cell Movement Specificity System Threonine Time Tyrosine Yeasts analog chromatin immunoprecipitation drug development fungus insight light microscopy mutant novel pathogen programs receptor receptor function transcription factor upstream kinase

中文摘要

翻译

描述（由申请人提供）：肺孢子虫是一种机会性真菌病原体，可引起艾滋病患者的重症肺炎（PCP）。在肺炎期间，肺孢子虫通过营养型和包囊增殖。调节肺孢子虫生命周期的机制还没有很好的定义，但是在密切相关的真菌中，信息素诱导的丝裂原活化蛋白激酶（MAPK）信号通路调节这一过程。我们的研究表明，卡氏疟原虫MAPK PCM，真菌信息素MAPK的直系同源物，补充酵母中的信息素信号。PCM的表达和活性大大增强营养型相比，包囊，暗示PCM活动在肺孢子虫的生命周期转变。我们已经发现PCM对生化激酶活性具有独特的要求，并且MAPK功能所需的典型磷酸化位点对于PCM激酶活性是不需要的。这些发现提示了PCM的新的调控机制，对PCM的进一步研究可能为病原真菌的信号通路提供新的见解。此外，我们已经确定了推定的信息素受体和转录因子的一部分，这MAPK途径在卡氏肺吸虫。在目前的建议中，我们假设信息素诱导的丝裂原活化蛋白激酶（MAPK）途径调节卡氏肺孢子虫的细胞分化和增殖。我们将通过三个独立但相互关联的具体目标来研究这些概念。通过这些研究，我们希望能够深入了解卡氏肺孢子虫的生物学特性，为治疗PCP的新药开发提供新的信息。

英文摘要

DESCRIPTION (provided by applicant): Pneumocystis is an opportunistic fungal pathogen which causes severe pneumonia (PCP) in patients with AIDS. During pneumonia, Pneumocystis proliferates through trophic forms and cysts. Mechanisms regulating the Pneumocystis life cycle are not well defined, however a pheromone-induced mitogen-activated protein kinase (MAPK) signaling pathway regulates this process in closely-related fungi. Our studies demonstrate that the P. carinii MAPK PCM, an ortholog to fungal pheromone MAPKs, complements pheromone signaling in yeast. PCM expression and activity are greatly augmented in trophic forms compared to cysts, implicating PCM activity in Pneumocystis life cycle transition. We have discovered that PCM has unique requirements for biochemical kinase activity, and the typical phosphorylation sites required for MAPK function are not needed for PCM kinase activity. These findings suggest novel regulation of PCM, the further study of which might provide insights into signaling pathways hi pathogenic fungi. Additionally, we have identified putative pheromone receptors and a transcription factor as part of this MAPK pathway in P. carinii. In the current proposal, we hypothesize that the pheromone-induced mitogen-activated protein kinase (MAPK) pathway regulates cellular differentiation and proliferation of P. carinii. We will investigate these concepts through three independent but interrelated Specific Aims. Through these investigations we hope to gain insights into P. carinii biology which may provide new information for novel drug development to treat PCP.

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