Figure 1.

Change in RAF isoform usage in response to a RAS mutation. In melanocytes, activation of cAMP not only stimulates melanogenesis but also inhibits the kinase CRAF. Therefore, BRAF activates the MAPK pathway downstream of RTKs in these cells. In melanomas containing a mutation of RAS, BRAF kinase is phosphorylated by ERK inhibiting its interaction with RAS. Hence, it is CRAF that activates the MAPK pathway downstream of RAS. Overexpression of PDE4 degrades cAMP preventing inhibition of CRAF by PKA. α-MSH: melanocyte stimulating hormone; MC1R: melanocortin-1 receptor, AC: adenylyl cyclase, PDE: phosphodiesterase, PKA: protein kinase A, CREB: cAMP responsive element binding protein, MITF: microphtalmia associated transcription factor; GF: growth factor; RTK: receptor tyrosine kinase.