MECHANISMS OF IONIC SIGNALING BY HEPATIC GROWTH FACTORS

申请人完全致力于以实验室为基础的职业生涯 调查，并设计了这一建议，以建立和扩大 在他的研究期间发展的技能和科学兴趣 训练本建议书中概述的研究将使申请人能够 把这个背景应用到对理解 激素信号转导和细胞调节方面 增殖 该项目的目的是研究肝细胞 响应生长因子的离子信号传导机制，特别是 确定生长因子激活的离子进入途径和机制 通过这种激活发生，并确定改变的作用， 离子流在调节原癌基因表达中作用， 生长因子反应。 实验设计采用了几种互补的方法来解决 总体目标。这些方法包括实时测量增长 因子诱导的细胞溶质阳离子浓度扰动， 负责此的离子电流的电生理检测 扰动，离子信号传导在调制中的作用的定义， 原癌基因表达和生长因子的表达克隆 激活的离子通道/转运蛋白。

The applicant is fully committed to a career in laboratory-based investigation and has designed this proposal to build upon and to broaden the skills and scientific interests developed during his fellowship training. The studies outlined in this proposal will enable the applicant to apply this background to questions that are fundamental to understanding aspects of hormonal signal transduction and regulation of cellular proliferation. The aim of the proposed project is to investigate the hepatocellular mechanisms of ionic signaling in response to growth factors, specifically to identify growth factor activated ion entry pathways and the mechanisms by which this activation occurs, and also to identify the role of altered ion flux in modulating proto-oncogene expression, an early downstream growth factor response. The experimental design employs several complementary approaches to address the overall goals. These approaches include real-time measurement of growth factor induced perturbations in cytosolic cation concentrations and electrophysiologic detection of ion currents responsible for this perturbation, definition of the role of ionic signaling in modulation of proto-oncogene expression, and expression cloning of growth factor activated ion channels/transporters in Xenopus oocytes.