Jackson J H, Li J W, Buss J E, Der C J, Cochrane C G
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12730-4. 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.
先前的研究表明，翻译后修饰对于致癌性K-ras 4B蛋白的膜结合和转化活性都是必需的。此外，汉考克等人[汉考克，J.F.，帕特森，H.和马歇尔，C.J.（1990年）《细胞》63卷，第133 - 139页]发现，K-ras 4B C末端包含的一个多聚赖氨酸结构域对于K-ras 4B的膜结合也是绝对必需的，但令人惊讶的是，无论是多聚赖氨酸结构域还是膜结合对于转化活性都不是必需的。我们进行了类似的研究，但我们的结果明显不同。我们的研究表明，多聚赖氨酸结构域对于K-ras 4B的转化活性至关重要。此外，我们证明，尽管多聚赖氨酸结构域增加了K-ras 4B的膜结合，但在没有该结构域的情况下也能发生大量的膜结合。最后，虽然我们的研究与K-ras 4B转化活性需要膜结合这一观点一致，但我们表明，膜结合本身并不足以实现高效的K-ras 4B转化活性。
