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Fig. 3 | Molecular Autism

Fig. 3

From: TSC patient-derived isogenic neural progenitor cells reveal altered early neurodevelopmental phenotypes and rapamycin-induced MNK-eIF4E signaling

Fig. 3

Activation of MEK/ERK and MNK-eIF4E pathways in TSC1 mutant NPCs. a In addition to mTORC1/2 activation, immunoblotting also showed Increased phosphorylation of ERK1/2 (pERK1/2) in TSC1-Het and Null NPCs. As predicted, rapamycin (100 nM, 24 h) inhibited mTORC1 signaling (pS6K and pS6 readouts). Rapamycin increased pERK1/2 in TSC1-Null NPCs; n = 5. b Treatment with rapamycin (100 nM, 24 h) leads to increased phosphorylation of translational subunit eIF4E (p-eIF4E) in TSC1-NPCs; n = 6. c Treatment with a MEK inhibitor tramatinib (250 nM, 24 h) alone or combined with rapamycin (100 nM, 24 h) inhibits phosphorylation of ERK1/2 (pERK1/2) but has no effect on the translational subunit eIF4E; n = 3. d Increased p-eIF4E in TSC1-Het and Null NPCs is blocked using MNK inhibitor eFT508 (50 nM, 24 h), alone or combined with rapamycin (100 nM, 24 h); n = 3. Mean values ± S.D. of three separate experiments are shown, *p < 0.01, **p < 0.001 calculated with Student’s t test

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