POLYLYSINE DOMAIN OF K-RAS 4B PROTEIN IS CRUCIAL FOR MALIGNANT TRANSFORMATION

Previous studies have shown that posttranslational modifications are r equired for both oncogenic K-ras 4B protein membrane binding and trans forming activity. In addition, Hancock et al. [Hancock, J. F., Patters on, Il. and Marshall, C. J. (1990) Cell 63, 133-139] found that a poly lysine domain contained at the C terminus of K-ras 4B was also absolut ely essential for Ii-ras 4B membrane binding but, surprisingly, neithe r the polylysine domain nor membrane binding was required for transfor ming activity. We have performed similar studies, but our results are distinctly different, Our studies indicate that the polylysine domain is crucial for Ii-ras 4B transforming activity. Moreover, we demonstra te that although the polylysine domain increases K-ras 4B membrane bin ding, significant amounts of membrane binding can occur in the absence of this domain. Finally, while our studies are consistent with the no tion that membrane binding is required for K-ras 4B transforming activ ity, we show that membrane binding, in and of itself, is not sufficien t for efficient K-ras 4B transforming activity.