A role for Ras in v-Crk transformation.

The v-crk oncogene, identified as the transforming gene of the CT10 avian sarcoma virus, encodes an adaptor protein capable of transforming chicken embryo fibroblasts (CEFs). Because the Src homology 3 domain of v-Crk is capable of binding the Ras family guanine nucleotide exchange factors Sos and C3G, the contribution of cellular Ras to signaling by v-Crk was evaluated. NIH-3T3 cell lines stably expressing the v-crk oncogene exhibited a transformed phenotype similar to that of CT10-infected CEFs. Treatment of these cells with a farnesylation inhibitor, as well as coexpression of dominant negative Ras, caused morphological reversion of the v-Crk NIH-3T3 cells. Dominant negative Ras expression also inhibited colony formation in soft agar without affecting tyrosine phosphorylation of cellular proteins. Although elevation of basal Erk activity could be demonstrated in v-Crk-transformed CEFs, no significant elevation of basal Erk activity was observed in the v-Crk-transformed NIH-3T3 cells. This suggests that v-Crk requires Ras function for transformation of NIH-3T3 cells and may utilize a Ras effector other than Erk to maintain the transformed phenotype.