Fig. 9: A model for the regulation of the Hippo pathway and YAP by PR55α.

Black lines indicate a current understanding of the Hippo signaling cascades that regulate YAP phosphorylation and stability, resulting in YAP cytoplasmic retention by 14-3-3 and proteasomal degradation by SCF(β-TrCP). Red lines indicate the novel findings presented in this report, showing that PR55α inhibits the MOB1-activated LATS1-S909/LATS2-S872 autophosphorylation that prevents YAP activation, while PR55α concomitantly inhibits YAP phosphorylation, both of which lead to YAP activation. Blue dotted lines indicate that PR55α activates MST1/2 levels and phosphorylation through an unknown mechanism