Mutations of C-RAF Are Rare in Human Cancer because C-RAF Has a Low Basal Kinase Activity Compared with B-RAF

摘要: The protein kinase B-RAF is mutated in ∼8% of human cancers. Here we show that presumptive mutants the closely related kinase, C-RAF, were detected only 4 545 (0.7%) cancer cell lines. activity two proteins not significantly different from wild-type C-RAF and these variants may represent rare polymorphisms. basal B-RAF–stimulated activities a third variant are unaltered but its activation by RAS reduced, suggesting it act dominant-negative manner to modulate pathway signaling. fourth has elevated hypersensitive does transform mammalian cells. Furthermore, when introduce equivalent most common mutation (V600E) into weak effect on convert an oncogene. This lack occurs because lacks constitutive charge within motif domain called N-region. fundamental difference RAF isoform regulation explains why frequently whereas mutations rare.