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G Protein-Mediated Gene Regulation

G蛋白介导的基因调控

基本信息

批准号：
7434755
负责人：
JEFFREY A HADWIGER
金额：
$ 2.31万
依托单位：
OKLAHOMA STATE UNIVERSITY STILLWATER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2009-06-30
项目状态：
已结题

项目摘要

G protein-coupled receptors detect many different external signals including ones that regulate gene expression and cellular differentiation. While many components of G protein-mediated signal transduction pathways are known, the mechanisms by which different signals regulate specific genes remains to be determined. Pathway specificity is in part determined by the G protein G(alpha) subunits and recent data indicate these subunits play a role in gene regulation in the soil amoebae Dictyostelium. The goal of the proposed research is to test the hypothesis that G(alpha) subunits regulate gene expression through interactions with other signaling components, such as MAP (mitogen-activated protein) kinases. To achieve this goal, the early developmental expression of discoidin (Dsc) in Dictyostelium will be examined in cells lacking the MAP kinase Erk2 and expressing different wild-type or chimeric G(alpha) subunits. In addition, a genetic screen will be used to identify suppressor mutations that rescue pDSC/GFP reporter gene expression from the repression of a chimeric G(alpha) subunit. The suppressor mutations will be created by REMI mutagenesis, allowing genes to be tagged that might function downstream of G(alpha) subunits to regulate gene expression. Additional characterization of suppressor genes will be conducted to verify their function regulating DSC gene expression downstream of G(alpha) subunits in these signaling pathways. These studies will provide significant insights into the signaling mechanisms that control the differentiation of eukaryotic cells.

G 蛋白偶联受体检测许多不同的外部信号，包括调节基因的信号表达和细胞分化。虽然 G 蛋白介导的信号转导的许多成分途径已知，但不同信号调节特定基因的机制仍有待了解决定。通路特异性部分由 G 蛋白 G(α) 亚基和最新数据决定表明这些亚基在土壤变形虫盘基网柄菌的基因调控中发挥作用。的目标拟议的研究是为了检验 G(α) 亚基通过调节基因表达的假设与其他信号成分的相互作用，例如 MAP（丝裂原激活蛋白）激酶。到为了实现这一目标，将检查盘基网柄菌中盘基蛋白 (Dsc) 的早期发育表达在缺乏 MAP 激酶 Erk2 并表达不同野生型或嵌合 G(α) 亚基的细胞中。在此外，基因筛选将用于识别拯救 pDSC/GFP 报告基因的抑制突变嵌合 G(α) 亚基的抑制导致基因表达。抑制突变将是由 REMI 诱变产生，允许标记可能在 G(alpha) 下游发挥作用的基因调节基因表达的亚基。将进行抑制基因的额外表征验证它们在这些信号传导中调节 G(α) 亚基下游 DSC 基因表达的功能途径。这些研究将为控制信号传导机制提供重要的见解。真核细胞的分化。