The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification

Homeostasis of multicellular organisms is critically dependent on the corre ct interpretation of the plethora of signals which cells are exposed to dur ing their lifespan. Various soluble factors regulate the activation state o f cellular receptors which are coupled to a complex signal transduction net work that ultimately generates signals defining the required biological res ponse. The epidermal growth factor receptor (EGFR) family of receptor tyros ine kinases represents both key regulators of normal cellular development a s well as critical players in a variety of pathophysiological phenomena. Th e aim of this review is to give a broad overview of signal transduction net works that are controlled by the EGFR superfamily of receptors in health an d disease and its application for target-selective therapeutic intervention . Since the EGFR and HER2 were recently identified as critical players in t he transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechani sms and significance of the interconnectivity between heterologous signalli ng systems.