Figure 6.

A model depicting the phosphorylation-modulated activity regulation of Merlin. (A, B) PAK1 can enhance phosphorylation of Merlin (A), and cause the inactivation of the Hippo-YAP signaling pathway as evidenced by increased expression levels of two YAP target genes CTGF and Cyr61 (B), presumably due to the weakened AMOT/phosphor-Merlin interaction. (C) A model depicting the phosphorylation-mediated activity regulation of Merlin. In this model, WT-Merlin adopts a semi-open conformation via an intra-molecular head-to-tail interaction. Upstream regulators such as AMOT can bind to Merlin-CTD, fully expose the FERM domain and thus activate Merlin. Phosphorylation of Ser518 can weaken AMOT's binding to Merlin-CTD and thus maintain Merlin in its inactive state.