Polylysine domain of K-ras 4B protein is crucial for malignant transformation.
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.
Jackson
J H
JH
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Li
J W
JW
Buss
J E
JE
Der
C J
CJ
Cochrane
C G
CG
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D066298:In Vitro Techniques; D008239:Lysine; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D016283:Proto-Oncogene Proteins p21(ras); D008239:Lysine