Figure 6

Different AKAPs compete to bind PKA based on cAMP-dependent or independent mode of PKA activation. FET cells treated with GF showed an effective increase in the association of Praja2 and RII subunit of PKA (PKARIIα) and a decrease in PKARII/Praja2 association when FET cells were treated with OSI-906. FET cells treated with OSI-906 showed an effective increase of AKAP149and PKARIIα association whereas an effective decrease in this association was observed when cells were treated with GF (A). OSI-906-mediated PKA activation requires AKAP149association with PKA as determined by knockdown of AKAP149in FET cells. PKA activation by GF treatment requires Praja2 association with PKA as determined by knockdown of Praja2 in FET cells (B). AKAP149is associated with negative regulation of IAPs survivin and XIAP as determined by knockdown of AKAP149in FET cells (C). Praja2 is associated with positive regulation of survivin and XIAP as determined by knockdown of Praja2 in FET cells (D). All experiments were repeated three times independently with 3 replicas per repeat for the ANOVA analysis (* P < 0.001).