Oncogenic mutations in B-Raf: some losses yield gains.
A study by Wan et al. in this issue of Cell demonstrates that the majority of oncogenic mutations in the B-Raf protein kinase result in increased catalytic activity, through disruption of the autoinhibited state of the kinase domain. Surprisingly, several mutations lead to impaired B-Raf kinase activity, yet these mutants are nevertheless capable of stimulating downstream signaling through transactivation of C-Raf.
Hubbard
Stevan R
SR
Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
D000818:Animals; D020134:Catalytic Domain / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf