BRAF and cancer: This configuration of the NtA motif primes BRAF for activation, which may explain why single mutations of BRAF, such as V600E in the activation loop, can cause full activation and drive cancer, while RAF1 mutations are rare in cancer.9 There is no consensus on which kinase phosphorylates the NtA motif in vivo, since several kinases, including RAF1 itself, have been reported to be able to do this.1, 10 As shown by mutagenesis studies,7 the NtA motif in the activator is required for transactivation of the receiver in RAF dimers.