A combined genetic and biochemical approach to mammalian signal transduction

The last five years have seen a rapid increase in interest and understanding of signal transduction pathways. While the description of such pathways has become more detailed and complex, a number of consistent findings have emerged. Modular domains, such as SH2 and SH3 domains, are present on a wide variety of proteins and mediate specific protein-protein interactions. By defining the interaction mediated by such domains, a 'language' of interaction between proteins in signalling pathways is emerging. As more signalling proteins are identified it has become apparent that most oncogenes and tumour suppressor genes are components of major signalling pathways. Therefore, studies on the basic biology of signal transduction are having a direct impact on our understanding of cell transformation. With the characterisation of signalling pathways in a range of organisms, it has also become obvious that signalling pathways are ancient and have been highly conserved over the last billion years of evolution. A practical result of this finding has been the ability to exploit results obtained in genetically tractable invertebrate species such as C. elegans and Drosophila melanogaster to investigate signal transduction in mammals. This is an approach we have emphasized in our investigation of signal transduction by tyrosine kinase receptors in human and mouse cells. Results obtained in these studies with the Sos and Siah proteins are reviewed.