Nuclear epidermal growth factor receptor (EGFR) signaling network in the heart

心脏中的核表皮生长因子受体 (EGFR) 信号网络

• 批准号: 311690-2007
• 负责人: Anderson, Hope
• 金额: $ 2.19万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=365455
• 关键词: Nuclear; epidermal; growth; factor; receptor

The proposed research investigates new signal pathways in the heart.  Specifically, we will study the Epidermal Growth Factor Receptor.  The EGFR is a protein that plays an important role in normal development, growth, mechanical sensing, and signaling pathways in the heart.  The novel aspect of our research is that we will be studying the EGFR in the nucleus of heart muscle cells.  The nucleus is the cell compartment which contains chromosomes.  Using a combination of sophisticated microscopy and biochemical assays, we will first confirm that the EGFR does localize to the nucleus of heart muscle cells.  Second, because the EGFR participates in heart development and growth, we will examine the effect of growth stimuli such as stretch or hormones on the activity of the EGFR.    We will then focus our attention on how the EGFR moves from the cell membrane to the nucleus.  The experiments that we have designed will determine how the EGFR is internalized into the cell, and whether other proteins help to shuttle the EGFR through the cell to the nucleus.  Finally, since the nucleus is the cell organelle in which genes are expressed, we will determine whether EGFR found in the nucleus of heart cells influences gene expression.Our research will advance our understanding of how signals are transmitted in the nucleus of heart muscle cells, which represents a new and exciting mechanism by which gene expression in the heart might be regulated.

拟议的研究调查了心脏中的新信号通路。  具体来说，我们将研究表皮生长因子受体。  EGFR 是一种在心脏正常发育、生长、机械传感和信号传导通路中发挥重要作用的蛋白质。  我们研究的新颖之处在于我们将研究心肌细胞核中的 EGFR。  细胞核是含有染色体的细胞室。  结合先进的显微镜和生化检测，我们将首先确认 EGFR 确实定位于心肌细胞的细胞核。  其次，由于 EGFR 参与心脏发育和生长，我们将检查生长刺激（例如拉伸或激素）对 EGFR 活性的影响。    然后我们将重点关注 EGFR 如何从细胞膜移动到细胞核。  我们设计的实验将确定 EGFR 如何内化到细胞中，以及其他蛋白质是否有助于将 EGFR 通过细胞运送到细胞核。  最后，由于细胞核是基因表达的细胞器，我们将确定心脏细胞核中发现的 EGFR 是否影响基因表达。我们的研究将加深我们对心肌细胞核中信号如何传递的理解，这代表了一种新的、令人兴奋的机制，心脏中的基因表达可能受到调节。