IGF2 acts as a secreted ligand, binding to and activating the IGF1 receptor. The predominant downstream effector of the activated IGF1 receptor is the kinase Akt, which plays multiple roles in survival and proliferation. We have previously shown that Akt cooperates with Shh signaling to promote proliferation through stabilization of N-myc (Kenney et al 2004). Akt activity has been linked to abrogation of the G2/M checkpoint after irradiation, through inactivation of ATM/Chk2 (Hirose et al 2005, Kandel et al 2002). Consistent with increased IGF1 receptor activity in response to IGF2 secretion, YAP-Smo-driven medulloblastomas exhibit higher levels of activated Akt (S473-phosphorylated), most notably in cells surrounding the vasculature (Figure 5G); interestingly, these cells also express the highest levels of YAP and they have been proposed to function as tumor repopulating cells after irradiation (Fernandez et al 2009, Hambardzumyan et al 2008). Taken together these observations raise the possibility that YAP-mediated IGF2 induction not only promotes survival and proliferation through Akt activation but may also affect the phosphorylation of ATM/Chk2, resulting in disruption of the G2/M checkpoint.