Fig 3.

NF1 and NF2 genes/proteins. (A) The NF1 gene encodes a 2818 amino acid protein with a central RAS-GTPase-activating protein domain. Neurofibromin functions to accelerate the conversion of active GTP-bound RAS to its inactive GDP-bound conformation. Active RAS transmits its growth-promoting signal by activating MEK, AKT, and mechanistic target of rapamycin (mTOR). (B) The NF2 gene encodes a 595 amino acid protein with striking sequence similarity to molecules of the protein 4.1 (ezrin, radixin, and moesin) superfamily. Numerous mechanisms have been proposed for merlin growth regulation, including suppression of RAF/MEK, YAP, mechanistic target of rapamycin (mTOR), ErbB2, Src, FAK, and Rac1 activation. Molecularly targeted therapies that inhibit specific signaling intermediates and receptor tyrosine kinases have been evaluated in preclinical and clinical trials.