Fig. 4
(A) Signaling downstream affected by various BRAF mutants. (a). Class I mutations activate MEK/ERK via monomeric BRAF with sustained signaling. (b). Class II mutants form dimers through BRAF and/or CRAF, activating the MAPK pathway. (c). Class III BRAF mutants display minimal or no kinase activity. Despite this, they increase interactions with RAS, leading to the activation of subsequent signaling pathway via dimer formation. (B) BRAF gene fusions lead to the loss of serine/threonine kinase domains while preserving the conserved region 3 (CR3) of the N-terminal ___domain. The absence of the N-terminal structural domains CR1 and CR2 is often offset by the presence of fusion partners, such as KIAA 1549. Truncation of the CR1 auto-inhibitory ___domain leads to the formation of constitutively active BRAF dimers and subsequently activate downstream signalling pathways.
