Figure 7

En2 modulates IGF1’s pleiotropic effects in GNPs, potentially through altered S6 kinase activation. While En2 expression appeared to have no effect on IGF1 activation of the PI3K pathway at the level of Akt phosphorylation, the absence of En2 caused increased phosphorylation of S6 kinase. Thus, we propose a model in which En2 expression in postnatal GNPs promotes differentiation and inhibits proliferation via disruption of S6 kinase activation, a well-characterized promitogenic signal. Potential targets for En2 may include PDK1 and mTORC1, which directly phosphorylate S6K, though these interactions remain to be explored. Alternatively, En2 may alter feedback inhibition between the S6K and the PI3K pathway. Dashed lines signify indirect pathways. Arrows and (+) indicate activation. Flat head and (-) indicate inhibition. GNP = Granule neuron precursor. IGF1R = Insulin-like growth factor-1 receptor. P = Phosphorylation.