| RESULTS : Here , using a series of NF 2 constructs , we show that NF 2 inhibits directly the Rac / CDC42 dependent Ser / Thr kinase PAK 1 , which is essential for both Ras transformation and neurofibromatosis type 1 ( NF 1 ) , through two separate domains . ^^^ A mutant of NF 2 , that lacks the PAK 1 inhibiting domain of 78 amino acids ( NF78C , residues 447 524 ) , fails to suppress Ras transformation . ^^^ Furthermore , PAK 1 specific inhibitors CEP 1347 and WR PAK 18 selectively inhibit the growth of NF 2 deficient cancer cells , but not NF 2 positive cells . ^^^ CONCLUSIONS : These results suggest that PAK 1 is essential for the malignant growth of NF 2 deficient cells , and that PAK 1 blocking drugs could be potentially useful forthe treatment of neurofibromatosis types 2 , in addition to Ras induced cancers and neurofibromatosis type 1 . . ^^^ |