Figure 1.

Schematic representation of the signaling pathways involved in NF1 tumorigenesis. Neurofibromin positively regulates adenylyl cyclase to increase intracellular cAMP levels which inhibits glial cell proliferation and survival. Also, neurofibromin promotes the conversion of active GTP-bound RAS to its inactive GDP-bound conformation. In NF1, the increased RAS activity in astrocytes leads to cell proliferation through the downstream activation of the PI3K/AKT/mTOR and RAF-MAK/MEK pathways.