The wild-type Ras: road ahead

The cellular Ras is known to play an important role in cellular proliferation mediated by growth factor receptor. Evidence also points to its role in growth arrest. Substantiated proof for growth-suppressive activity of wild-type Ras comes from studies that showed 1) loss of wild-type ras allele in tumors, 2) suppression of growth in cells transformed by oncogenic ras upon overexpression of wild-type Ras, and 3) up-regulation of Ras expression during postnatal development and following growth arrest of untransformed cells in culture. To understand the mechanism by which the wild-type Ras brings about these diverse actions, we evaluated its well-known role in actively proliferating cells and its less understood role in growth arrest. This led to the proposal that wild-type Ras in either GDP GTP-bound state can antagonize the function of oncogenic Ras.