CRITICAL ROLE OF RHO IN CELL-TRANSFORMATION BY ONCOGENIC RAS

We demonstrate that Rho, a regulator of cytoskeletal actin, is necessa ry for Ras transformation. A dominant inhibitory Rho gene (RhoB(N19)) specifically suppressed Rat1 cell focus formation induced by oncogenic Ras but not by Raf. An activated Rho gene (Rho(V14)) lacked focus for mation activity but augmented the focus formation activity of both onc ogenes. NIH3T3 cell lines expressing Rho(V14) grew to higher saturatio n density and displayed reduced serum and anchorage requirements for g rowth. We concluded that Rho played a role in cell growth regulation a nd was required for transformation by oncogenic Ras but not Raf. A mod el for Ras signal transduction proposing separate Rho-dependent and Ra f-dependent pathways is discussed.