Skip to main content
. 2018 Mar 21;20(9):1185–1196. doi: 10.1093/neuonc/noy046

Fig. 3.

Fig. 3

Independent activation of the mTOR and EPH receptor pathways in NF2-null ACs and inhibition of EPHA2(S897) phosphorylation by MEK inhibitors. (A) AC-CRISPR lines (NF2+ and NF2−) treated for 24 h with rapamycin (20 nM) or AZD2014 (300 nM) show inhibition of mTORC1 (readouts: pS6K/pS6) and mTORC2 (readouts: pAkt/pNDRG1) signaling with no effect on EPHA2, EPHB1, c-KIT, or Src/SFK. Dasatinib (100 nM, 24 h) attenuates pEPHA2, pEPHB1, c-KIT, and pSrc/SFK with modest effects on mTORC1/2 signaling. (B) EPHA2 inhibitor ALW-II-41-27 (24 h) blocks pEPHA2, pEPHB1, and pSrc/SFK with no effect on mTORC2 signaling, while attenuating mTORC1 signaling. (C) Treatment of NF2− ACs with AZD6244 (1 µM, 2 h) inhibits pEPHA2(S897), while MK2206 (1 µM) did not. (D) Treatment of NF2− ACs for 24 h with AZD6244 or trametinib inhibits pEPHA2(S897) and pERK1/2 while increasing phospho- and total Src/SFK.