Determinants of Smoothened Activity

平滑活动的决定因素

• 批准号: 6888903
• 负责人: ELIZABETH H WILLIAMS
• 金额: $ 4.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6888903
• 关键词: Drosophilidae; RNA interference; alleles; biological signal transduction; cell surface receptors; chemical genetics; enzyme activity; genetic screening; kinesin; membrane proteins; phosphoprotein phosphatase; phosphorylation; postdoctoral investigator; protein binding; protein kinase; protein localization; protein protein interaction; protein purification; protein sequence; protein signal sequence; protein structure function; site directed mutagenesis; transcription factor

DESCRIPTION (provided by applicant): The Hedgehog (Hh) signaling pathway plays an essential and evolutionarily conserved role in patterning the embryonic body plan and in maintaining the proliferative status of adult cell populations. Inappropriate regulation of Hh signaling in vertebrates can lead to developmental defects and to multiple spontaneous and inherited cancers. One of the Hh pathway components implicated in the development of cancer is the transmembrane protein Smoothened (Smo). Smo is a primary determinant of Hh pathway activity, but the mechanism by which Smo mediates Hh signaling is not well understood. To identify the sequences necessary for Smo hyperphosphorylation, interaction with the downstream effector molecule Costal-2 (Cos2), and subcellular localization and to analyze the functional relevance of these events in Hh signaling, mutagenesis and biochemical characterization of Smo alleles will be conducted to map functional domains of Smo within its protein structure, and the cellular mediators of Smo phosphorylation will be identified and characterized through genetic and biochemical screening.

描述（由申请人提供）： 刺猬（HH）信号通路在模仿胚胎身体计划和维持成年细胞群体的增殖状态方面起着至关重要的进化作用。脊椎动物中HH信号传导的不当调节会导致发育缺陷，并导致多种自发和遗传的癌症。与癌症发展有关的HH途径成分之一是跨膜蛋白平滑（SMO）。 SMO是HH途径活性的主要决定因素，但是SMO介导HH信号传导的机制尚不清楚。要确定SMO高磷酸化所需的序列，与下游效应分子costal-2（COS2）和亚细胞定位的相互作用，并分析这些事件在HH信号传导，诱变，诱变和生物化学特征中的功能相关性，以绘制其在SMO等位基因的范围内，以绘制其在其蛋白质结构中的识别范围，并在其pypliate smo中识别smo smo的构图，并将其构图构成覆盖范围的构建机构，并将其构造覆盖范围覆盖范围，并将其构成覆盖层的构建范围，并将其构成覆盖层的构建范围。通过遗传和生化筛查来表征。