Signaling Mechanisms and Mobility of the EGF Receptor

点击翻译按钮获取中文摘要

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.