| Modification Notes |
It is well established that Ras oncogenes have a central role in the pathogenesis of a broad range of malignancies (1). However, their mechanism of action is unclear. All members of the ras oncogene family encode proteins that bind the guanine nucleotides GDP and GTP and can hydrolyze bound GTP (1). These proteins are members of a much larger family of GTPases that are involved in the regulation of many cellular pathways (2-6) and are themselves regulated by a GTPase-activation protein (GAP) (5,6). In mitogenically activated and tyrosine kinase-transformed cells, Ras GAP forms a complex with a protein designated p190. p190 at its amino terminus contains sequence motifs characteristic of all known GTPases while the carboxy terminal domain contains sequences similar to those found in the Bcr gene product and n-chimeric and Rho GAP, all of which exhibit intrinsic GAP activity (7). In addition, the central domain of p190 contains a sequence nearlyidentical to that of the transcriptional repressor, GRF-1 (7). |
