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

这项拟议的研究探讨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、机械传感和信号通路中起重要作用的蛋白质。我们研究的新颖之处在于我们将研究心肌细胞细胞核中的EGFR。细胞核是包含染色体的细胞室。使用复杂的显微镜和生化分析相结合，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，我们将研究生长刺激（如拉伸或激素）对EGFR活性的影响。然后我们将把注意力集中在EGFR如何从细胞膜转移到细胞核上。我们设计的实验将确定EGFR如何内化到细胞中，以及是否有其他蛋白质帮助将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，我们将确定在心脏细胞核中发现的EGFR是否会影响基因表达。我们的研究将促进我们对信号如何在心肌细胞核中传递的理解，这代表了一种新的令人兴奋的机制，通过这种机制，心脏中的基因表达可能被调节。

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.