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Chunk #16 — RESULTS — Modulation of AKT signaling by DISC1 through its interaction with KIAA1212

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DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212.
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How does DISC1 binding to KIAA1212 suppress the activation of AKT signaling? We examined interaction among KIAA1212, AKT and DISC1. Consistent with previous reports (Anai et al., 2005; Enomoto et al., 2005), co-IP analysis suggested that HA-KIAA1212 expressed in HEK293 cells was associated with endogenous AKT (Figure 3B). HA-KIAA1212 and DISC1 were also associated with each other with or without insulin treatment (Figure 3C). Interestingly, co-expression of DISC1 and KIAA1212 inhibited the association between KIAA1212 and endogenous AKT in HEK293 cells (Figure 3B). In addition, no strong association between DISC1 and endogenous AKT was detected in the presence or absence of either insulin treatment or KIAA1212 overexpression in HEK293 cells (Figure 3D), suggesting a lack of high-affinity direct interaction between DISC1 and AKT.