Using the Neurofibromatosis Tumor Predisposition Syndromes to Understand Normal Nervous System Development
Neurofibromin structure and function. (a) Neurofibromin is a 2,818-amino-acid cytoplasmic protein with three alternatively spliced exons (9a, 23a, and 48a) and a central GAP-related domain (GRD). GAPs are negative regulators of RAS by accelerating the conversion of active GTP-bound RAS to its inactive GDP-bound form. (b) Loss of neurofibromin function leads to increased RAS pathway (RAF/MEK/ERK or PI3K/AKT/mTOR) signaling as well as reduced cAMP generation.