MUTATIONS IN THE V-MOS GENE ABOLISH ITS ABILITY TO INDUCE DIFFERENTIATION BUT NOT TRANSFORMATION

The v-mos oncogene product has the ability to induce differentiation i n human monocytic leukemia U937 cells, thereby arresting cell prolifer ation, and also exhibits transforming activity in mouse NIH3T3 cells. Mutation in the v-mos gene consisting of one or two amino acid substit utions in the putative ATP-binding domain impaired its differentiation -inducing activity although mutant proteins showed rather higher level s of autophosphorylation in vitro. Macrophage-specific characteristics such as their morphology, expression of C3b receptor and Fc receptor, and production of interleukin-1 beta and tumor necrosis factor alpha, were equally diminished in cells transfected with mutant mos genes wh en compared to those with intact v-mos. The ability of the gene to arr est the proliferation of U937 cells was likewise diminished, while the transforming efficiency of the intact and mutant mos genes mere essen tially the same. These results suggest that the mos product functions differently in cell differentiation and transformation.