The Epidermal Growth Factor Family of Ligands and Receptors Grows and Grows

Excerpt

Since the sequence of the human genome became available it has been clear that there are four members of the Epidermal Growth Factor receptor family. The HER4 gene is however subject to splicing to produce at least four full length receptor products with varying properties and functions. Defining a limit for the number of ligands is more problematic but there are clearly a minimum of 11 genes. In the case of the Neuregulins 1–4 they are spliced to give a daunting complex array of alternative gene products with unexpected sub-cellular locations and possible functions. Despite this growth in our knowledge in the composition of this highly interactive family it is still not uncommon to see references to “the EGF receptor and its ligands EGF and TGFalpha” in some review articles. This volume goes some way forward in reinforcing the reality that this is a highly complex family of molecules which have critical roles in breast development and in disease. Indeed the work described represents many paradigms which may well apply to less studied receptor tyrosine kinases. The system can be viewed as a computational device existing in cell membranes capable of receiving and integrating a wide array of signals and producing a variety of possible cellular responses. The components of the system, unlike in an electronic computer can vary in expression levels under natural conditions and aberrant over expression or mutational activation can perturb cell behaviour making significant contributions to the carcinogenesis process. …