ACTIVATION OF RAF AS A RESULT OF RECRUITMENT TO THE PLASMA-MEMBRANE
ACTIVATION OF RAF AS A RESULT OF RECRUITMENT TO THE PLASMA-MEMBRANE
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DOI：
10.1126/science.7811320
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发表时间：
1994-06-03
期刊：
影响因子：
56.9
通讯作者：
HANCOCK, JF
中科院分区：
文献类型：
--
作者：
STOKOE, D;MACDONALD, SG;HANCOCK, JF
小鸟嘌呤核苷酸结合蛋白Ras参与促进生长的信号转导途径。研究了Ras与蛋白激酶Raf相互作用导致Raf活化的机制。Raf通过加入K-ras的羧基端定位信号而靶向质膜。这种Raf的修饰形式（RafCAAX）被激活到与致癌突变Ras共表达的Raf相同的程度。质膜定位，而不是法尼基化或额外的COOH-末端序列的存在下占RafCAAX的激活。RafCAAX的激活完全不依赖于Ras，既不被致癌突变体Ras增强，也不被显性负性Ras消除。Raf一旦被招募到质膜上，就不会被Ras锚定在那里;细胞中大多数激活的Raf与质膜细胞骨架元素相关，而不是脂质双层。因此，Ras通过将Raf募集到质膜而在Raf的活化中起作用，在质膜处发生Raf的单独的、Ras非依赖性的活化。
The small guanine nucleotide binding protein Ras participates in a growth promoting signal transduction pathway. The mechanism by which interaction of Ras with the protein kinase Raf leads to activation of Raf was studied. Raf was targeted to the plasma membrane by addition of the COOH-terminal localization signals of K-ras. This modified form of Raf (RafCAAX) was activated to the same extent as Raf coexpressed with oncogenic mutant Ras. Plasma membrane localization rather than farnesylation or the presence of the additional COOH-terminal sequence accounted for the activation of RafCAAX. The acti vation of RafCAAX was completely independent of Ras; it was neither potentiated by oncogenic mutant Ras nor abrogated by dominant negative Ras. Raf, once recruited to the plasma membrane, was not anchored there by Ras; most activated Raf in cells was associated with plasma membrane cytoskeletal elements, not the lipid bilayer. Thus, Ras functions in the activation of Raf by recruiting Raf to the plasma membrane where a separate, Ras-independent, activation of Raf occurs.