Figure 3.

Schematic representation of the neurofibromin signalling pathways. Neurofibromin positively regulates adenylyl cyclase which, converting ATP in cAMP, increases the intracellular cAMP levels with consequent inhibition of cell proliferation. In addition, neurofibromin promotes the conversion of active GTP-bound Ras to its inactive GDP-bound conformation. The downstream effectors of the Ras pathway include mitogen-activated protein kinase (MAPK) and the phosphatidylinositol-3-phosphate kinase (PI3K). The activation of these Ras-triggered pathways leads to cell proliferation and tumour growth. Therefore, neurofibromin—acting as a negative modulator of the Ras signalling—exerts a tumour suppressor activity. Figure was redrawn from Lobbous et al. [283].