| H-, K- and N-Ras genes encode 21 kDa guanine nucleotide-binding proteins. H-Ras and K-Ras were first identified as oncogenes of acutely transforming RNA tumor viruses. Subsequently, mutated Ras genes have been found in many human tumors, providing evidence for a common genetic target in cancer. Ras-encoded proteins bind to GDP and to GTP with high affinity and possess a low level of intrinsic GTPase activity that can be stimulated over 100-fold by interaction with cytosolic GTPase activating protein (GAP). M-Ras was identified as a GTPase that shares structural similarities to the Ras family proteins. In mammals, a variety of extracellular growth factors that act through protein tyrosine kinase receptors, such as insulin, platelet-derived growth factor and nerve growth factor, require Ras to exert their effects. Ras p21 in its active GTP bound state binds to Raf-1, resulting in activation of the MAP kinase signaling cascade. An additional member of the Ras family, Rheb (Ras-related GTP-binding protein), also interacts with Raf-1. This interaction is potentiated by growth factors and agents that increase cAMP levels. R-Ras and TC 21 (also designated R-Ras-2) are also members of the Ras family. |
