PAK1 inhibition also leads to attenuated mTORC1 but not mTORC2 signaling, suggesting that mTORC2/SGK1 and Rac1/PAK1 pathways are independently responsible for mTORC1 activation in NF2-deficient meningiomas.
The NF2-encoded protein Merlin is closely related to the Ezrin-Radixin-Moesin family of membrane/cytoskeleton linker proteins, and has been demonstrated to suppress tumor growth by inhibiting extracellular signal-regulated kinase (ERK) and Rac1 activation.
Recent work on the neurofibromatosis 2 (NF2) tumor suppressor gene suggests that this negative growth regulator might function by modulating growth factor and extracellular matrix (ECM) signals that trigger Rac1-dependent cytoskeleton-associated processes.