Signaling Mechanisms and Mobility of the EGF Receptor

该项目的重点是离子信号的调节， 在培养物中的促分裂原刺激的细胞。 表皮生长因子 (EGF)和细胞外ATP将作为促有丝分裂激动剂进行研究。 单个细胞离子信号将通过以下组合进行研究： 荧光探针成像和膜片钳电生理学。 将检查这些激动剂之间的异源相互作用。 信号转导的化学动力学结果 级联反应，从激活的受体通过G蛋白，脂肪酶，激酶， 和可溶性的第二信使，将被建模。 动力学 预测将与单细胞数据进行比较，以澄清 各种信号成分在时间响应中的作用 细胞内钙变化的模式，继主要 有丝分裂信号 本研究的重点是以下信号转导级联 表皮生长因子细胞受体的激活。 光学显微镜结合荧光指示剂 胞浆游离钙离子浓度和膜电位 将用于在单个细胞水平上研究这些因素。 建立了信号级联的数学模型 来帮助理解这一复杂的事件序列。 这项研究的结果将有助于了解 细胞对外部信号反应的分子基础 分子。

This project focuses on the regulation of ionic signaling in mitogen-stimulated cells in culture. Both epidermal growth factor (EGF) and extracellular ATP will be studied as mitogenic agonists. Individual cell ionic signals will be studied by a combination of fluorescent probe imaging and patch clamp electrophysiology. Heterologous interactions between these agonists will be examined. The chemical kinetic consequences of the signal transduction cascade, from activated receptor through G-protein, lipase, kinase, and soluble second messengers, will be modeled. Kinetic predictions will be compared with single cell data to clarify the roles of the various signaling components in the temporal response pattern of intracellular calcium changes subsequent to a primary mitogenic signal. This research focuses on the signal transduction cascade following activation of the cellular receptor for epidermal growth factor. Optical microscopy in combination with fluorescent indicators of cytosolic free calcium ion concentration and of membrane potential will be used to study these factors at the level of a single cell. A mathematical model of the signaling cascade will be constructed to aid in the understanding of this complex sequence of events. The results of this research will contribute to understanding of the molecular basis of the response of cells to external signaling molecules.