Morphology of ras-transformed cells becomes apparently normal again with tyrosine kinase inhibitors without a decrease in the ras-GTP complex

Radicicol, an inhibitor of protein-tyrosine kinase, was found to cause morphological reversion of v-Ha-rastransformed NIH3T3 fibroblasts and T24 human urinary bladder carcinoma cells that contain an activated rasmutation. The network of actin stress fihers was restored during the treatment with radicicol. A similar morphological change was observed with another protein-tyrosinc kinase inhibitor, herbimycin A. Radicicol did not cause any changes in the proportion of the active GTP binding form of p21^ms or, its subcellular localization. These results rule out the possibility that the morphological reversion by radicicol is due to direct or indirect inhibition of the p21^ms function. Cycloheximide and actinomycin D inhibited the morphological change by radicicol, suggesting that the induced transcription of a gene(s) followed by de novo protein synthesis is required for suppression of the transformed phenotype in ras-transformed cells by tyrosine kinase inhibitors.