Polylysine Domain of K-ras 4B Protein is Crucial for Malignant Transformation

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-12, Vol.91 (26), p.12730-12734
• Main Authors: Jackson, J. H., Li, J. W., Buss, J. E., Der, C. J., Cochrane, C. G.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Biochemistry; Cancer; Cell Compartmentation; Cell Membrane - metabolism; Cell membranes; Cell Transformation, Neoplastic; Cellular immunity; Cytosol; In Vitro Techniques; Lysine; Methylation; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Mutation; NIH 3T3 cells; P branes; Post translational modification; Protein Prenylation; Protein Processing, Post-Translational; Proteins; Proto-Oncogene Proteins p21(ras) - chemistry; Proto-Oncogene Proteins p21(ras) - metabolism; Rats; Structure-Activity Relationship
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.26.12730

Previous studies have shown that posttranslational modifications are required for both oncogenic K-ras 4B protein membrane binding and transforming activity. In addition, Hancock et al. [Hancock, J. F., Patterson, H. \& Marshall, C. J. (1990) Cell 63, 133-139] found that a polylysine domain contained at the C terminus of K-ras 4B was also absolutely essential for K-ras 4B membrane binding but, surprisingly, neither the polylysine domain nor membrane binding was required for transforming activity. We have performed similar studies, but our results are distinctly different. Our studies indicate that the polylysine domain is crucial for K-ras 4B transforming activity. Moreover, we demonstrate that although the polylysine domain increases K-ras 4B membrane binding, significant amounts of membrane binding can occur in the absence of this domain. Finally, while our studies are consistent with the notion that membrane binding is required for K-ras 4B transforming activity, we show that membrane binding, in and of itself, is not sufficient for efficient K-ras 4B transforming activity.