FIGURE 8:

Scheme of the mechanisms by which the lack of ZO-2 triggered cell hypertrophy. The absence of ZO-2 promoted an increase in cell size by two mechanisms: an increase in the time that the cells spent in the G1 phase of the cell cycle, and the accumulation of YAP at the nucleus, which promoted the transcriptional activity that triggered subsequent activation of the PI3K/Akt/mTORC1 complex and its downstream target, S6K1, which increased protein synthesis. The increased inhibitory phosphorylation of GSK3β due to Akt activation inhibited the interactions of the SAV/APC/LATS1 complex in the Hippo pathway and thereby reduced the phosphorylation of YAP and promoted its transcriptional activity. Purple arrows, changes observed in MDCK ZO-2 KD cells; blue arrows, cross-talk between YAP and PI3K/Akt signaling pathways; green arrows, GSK-3β regulation of β-catenin transcriptional activity and the Hippo pathway.