Genes and Oncogenes of the ras Superfamily

Abstract

The search for oncogenic sequences in human tumor DNA, using the DNA gene transfer technique for transformation of recipient cells, have repeatedly led to the rediscovery of one of the three closely related genes: H-ras, K-ras (first found as the cellular genomic sequences (oncogenes) transduced in the Harvey and Kirsten sarcoma viruses) and N-ras. The three ras genes code for 21kD GTP/GDP binding proteins; they are transiently anchored at the inner face of the plasma membrane upon reversible C-terminal farnesylation. Acquisition of a transforming potential is due to a point mutation that results in an amino acid substitution that most frequently occurs at positions 12, 13 or 61. Expression of such activated proteins causes dramatic changes (membrane ruffling, cell motility, etc…) and loss of contact inhibition. Ras proteins are highly conserved throughout evolution and are found in all eucaryotic organisms where they must exert essential functions. In spite of intense investigation the precise biochemical role of the ras proteins remains elusive(1).