MECHANISMS OF IONIC SIGNALING BY HEPATIC GROWTH FACTORS

申请者完全致力于实验室工作。 调查，并设计了这项建议，以此为基础和扩大 在他担任研究员期间发展起来的技能和科学兴趣 训练。本建议书中概述的研究将使申请者能够 将这一背景应用于对理解至关重要的问题 细胞内激素信号转导与调控的研究进展 扩散。 拟议的项目的目的是研究肝细胞 离子信号对生长因子的响应机制，特别是 确定生长因子激活的离子进入途径及其机制 这种激活发生的方式，也是为了识别改变的作用 离子通量在调控原癌基因表达中的作用 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。这些方法包括对增长的实时测量 因子诱导的胞浆阳离子浓度扰动和 对与此有关的离子电流的电生理检测 微扰，离子信号在调节中的作用的定义 原癌基因的表达及生长因子的表达克隆 非洲爪哇卵母细胞中激活的离子通道/转运体。

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.