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Unfarnesylated transforming Ras mutant inhibits the Ras‐signaling pathway by forming a stable Ras·Raf complex in the cytosol
Author(s) -
Miyake Mika,
Mizutani Shin,
Koide Hiroshi,
Kaziro Yoshito
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01416-0
Subject(s) - cytosol , anti apoptotic ras signalling cascade , chromosomal translocation , microbiology and biotechnology , mutant , farnesyltransferase , chemistry , signal transduction , biology , biochemistry , prenylation , enzyme , mapk/erk pathway , gene
Farnesyltransferase inhibitors cause the growth arrest of ras ‐transformed cells, but not that of normal cells. To elucidate the mechanism of this differential effect, we examined the effect of accumulation of unfarnesylated Ras in the cytosol by using Ras G12V,C186S and Ras C186S , which mimic unfarnesylated form of the oncogenic and the normal Ras, respectively. We found that Ras G12,C186S inhibited activation and membrane translocation of Raf by forming a stable complex with Raf in the cytosol. In contrast, Ras C186S showed inhibitory effect on neither Raf activation nor Raf translocation. These results indicate that unfarnesylated oncogenic Ras interacts with Raf in the cytosol and inhibits its membrane translocation, a crucial step for the Raf activation, while unfarnesylated normal Ras does not.