The ras Gene Family

Abstract

The ras gene family in mammalian cells consists of five closely related members: the Harvey and Kirsten ras genes (c-Ha-ras1 and c-Ki-ras2), an inactive pseudogene of each (c-Ha-ras2 and c-Ki-ras1; see Hall 1984) and the N-ras gene. There are also several distinctly related genes designated rho (ras-homologous; Madaule and Axel 1985). In addition to their sequence homology, the genes of the ras family are related by the fact that they encode protein products of approximately 21 kDa (p21 ras ) which share the properties of GTP/GDP binding, weak GTPase activity and the presence of C-terminal cysteine residues (potential palmitation sites for membrane localization). In the past several years, a growing body of evidence has implicated the ras genes as playing a role in a wide variety of human cancers. The evidence comes largely from studies indicating that approximately 10–20% of most types of human malignancies contain an “activated” ras oncogene which is capable of inducing transformed foci following transfer into recipient cells such as mouse NIH-3T3. This chapter discusses three aspects of the ras genes: gene structure and expression, mechanism of activation in human tumours, and biochemistry of the p21 ras protein. Additional aspects are covered in the chapters by Fasano and by Masters and Bourne in this Volume.