Nuclear exclusion and cytoplasmic retention of AKT-phosphorylated FOXO1 is promoted by binding of FOXO1 to 14-3-3 proteins: YWHAZ (14-3-3 zeta), YWHAQ (14-3-3 theta), YWHAB (14-3-3 beta) and YWHAG (14-3-3 gamma) (Rena et al. 2001).
Nuclear exclusion and cytoplasmic retention of AKT-phosphorylated FOXO3 is promoted by binding of FOXO3 to 14-3-3 proteins: YWHAZ (14-3-3 zeta), YWHAQ (14-3-3 theta), and SFN (14-3-3 sigma) (Brunet et al. 1999, Arimoto-Ishida et al. 2004).
Phosphorylation of TSC2 by AKT enables association of TSC2 with 14-3-3 proteins YWHAB (14-3-3 protein beta/alpha), YWHAQ (14-3-3 protein theta), YWHAG (14-3-3 protein gamma), YWHAH (14-3-3 protein eta), YWHAE (14-3-3 protein epsilon), YWHAZ (14-3-3 protein zeta/delta) or SFN (14-3-3 protein sigma) (Liu et al. 2002). Binding to 14-3-3 proteins sequesters TSC2 to the cytosol and prevents its association with TSC1 (Cai et al. 2006).
14-3-3 proteins bind BAD phosphorylated by activated AKT on serine residue S99 (corresponds to mouse Bad serine residue S136). Binding of 14-3-3 proteins to p-S99-BAD facilitates subsequent phosphorylation of BAD on serine residue S118 (corresponds to mouse serine S155), which disrupts binding of BAD to BCL2 proteins and promotes cell survival (Datta et al. 2000). Caspase-3 mediated cleavage of 14-3-3 proteins releases BAD and promotes apoptosis (Won et al. 2003). All known 14-3-3 protein isoforms (beta/alpha i.e. YWHAB, gamma i.e. YWHAG, zeta/delta i.e. YWHAZ, epsilon i.e. YWHAE, eta i.e. YWHAH, sigma i.e. SFN and theta i.e. YWHAQ) can interact with BAD and inhibit it (Subramanian et al. 2001, Chen et al. 2005).