RAS Family GTPases

It has been nearly four decades since the potent tumor-inducing Harvey and Kirsten murine sarcoma viruses were first discovered. Subsequently, it was the pioneering work by Scolnick and colleagues during the 1970’s that first established the identity of cellular Ras genes as oncogenes and their gene products as guanine nucleotide binding proteins. However, it was not until 1982, when mutationally activated forms of human Ras genes were found in human tumor cell lines that Ras became the subject of intense research to elucidate the genetic basis of cancer and to develop novel target-based cancer therapeutics. Since that time great advances have been made in our understanding of Ras function and biology. These advances include landmark discoveries implicating Ras proteins as key components in signal transduction and as the founding members of a large superfamily of small GTPases that number over 150 human proteins. This chapter will provide a historical prospective of the various aspects of Ras and Ras signaling that are the topics of this book