We next examined the potential role of DISC1 and KIAA1212 association in regulating AKT signaling. Treatment of HEK293 cells with insulin led to increased activation of AKT signaling as shown by significant elevation of pAKT and pS6 levels (Figure 3A). Insulin treatment also led to increased phosphorylation of KIAA1212 (pKIAA; Figure S5). Consistent with a role of KIAA1212 in potentiating AKT activation, over-expression of KIAA1212 led to an elevation of pAKT and pS6 levels in the absence of insulin treatment (Figure 3A). Interestingly, co-expression of DISC1 and KIAA1212 significantly suppressed pAKT and pS6 levels in response to either insulin treatment or after KIAA1212 expression (Figure 3A). Furthermore, phosphorylation of KIAA1212 was also diminished under these conditions (Figure S5). In contrast, expression of DISC1 alone without KIAA1212 overexpression did not appear to change the levels of pAKT and pS6 with or without insulin treatment (Figure 3A), suggesting a requirement of KIAA1212 for DISC1-dependent modulation of AKT signaling.
