Role of Src in signal transduction pathways. The Jubilee Lecture.

Src was the first oncogene to be discovered, and the first protein tyrosine kinase. The study of how Src transforms cells has been a rich field that has lead to insights into the control of the cell cycle, the organization of the cytoskeleton, and growth factor-independent growth. Yet we still do not fully understand exactly what Src does. In normal cells, Src has been implicated in the control of cell division, the production of autocrine growth factors, the cell's survival response, as well as in cell motility. My laboratory has focused on the involvement of Src and related kinases in the response of cells to mitogenic growth factors. We have shown that the activity of Src kinases is necessary for cells to enter the cell cycle when treated with mitogens such as platelet-derived growth factor. Src activity initiates a signal transduction cascade, involving the adaptor protein Shc, which culminates in the transcriptional activation of the transcription factor Myc. Furthermore, we have also shown that this requirement for Src is abrogated in cells lacking the tumour suppressor p53, suggesting that another of Src's functions in normal cells is to suppress the actions of p53.