Roles for G Proteins in Wnt/Frizzled Signaling

G 蛋白在 Wnt/卷曲信号传导中的作用

• 批准号: 6693747
• 负责人: TIMOTHY A FIELDS
• 金额: $ 11.64万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693747
• 关键词: Roles; Proteins; Wnt; Frizzled; Signaling

DESCRIPTION (provided by applicant): The Wnt family of proteins are secreted signaling molecules that regulate a number of critical developmental processes, including cellular proliferation and differentiation. Moreover, aberrant activation of the Wnt signaling pathway has been shown to be an important component in oncogenesis. Wnt signaling is very complex and is initiated by a family of transmembrane heptahelical receptors known as Frizzled, which are most closely related to the family of G protein coupled-receptors. Despite evidence implicating G proteins in Wnt/Frizzled signal transduction, the precise mechanism by which Frizzled receptors choose downstream targets and transmit signals to them is still unclear. In this application, I propose to identify specific Frizzled/G protein interactions to test the hypothesis that Frizzled receptors are, in fact, G protein-coupled receptors. In addition, I will attempt to define the role of G proteins in determining Wnt/Frizzled signaling pathway choices and in linking Frizzled to known downstream target molecules such as Axin. The proposed project will be undertaken with the mentorship of Dr. Patrick J. Casey and Dr. Robert J. Lefkowitz and with the support of the Department of Pathology at Duke University. My background in protein biochemistry and G protein signaling provides a solid foundation for initiating these studies. This award will allow me to develop skills necessary to progress to the study of more biological aspects of cell regulation and will facilitate my transition to an independent investigator.

描述（由申请人提供）： 蛋白质的Wnt家族是分泌的信号分子，可调节许多关键发育过程，包括细胞增殖和分化。此外，Wnt信号通路的异常激活已被证明是肿瘤发生的重要组成部分。 Wnt信号传导非常复杂，是由称为毛躁的跨膜七向受体家族引发的，该家族与G蛋白偶联受体家族最密切相关。尽管有证据表明在Wnt/卷曲的信号转导中含有G蛋白，但仍不清楚毛躁受体选择下游靶标和传递信号的确切机制仍不清楚。在此应用中，我建议识别特定的毛躁/G蛋白相互作用，以测试毛茸茸的受体实际上是G蛋白偶联受体的假设。此外，我将尝试定义G蛋白在确定Wnt/毛躁的信号通路选择中的作用，以及将毛躁与已知的下游目标分子（如Axin）连接起来。拟议的项目将在帕特里克·J·凯西（Patrick J.我在蛋白质生物化学和G蛋白信号传导方面的背景为启动这些研究提供了坚实的基础。该奖项将使我能够发展出必要的技能，以研究细胞调节的更多生物学方面，并促进我向独立研究者的过渡。