Figure 7.

Hypothetical model of merlin's role on inhibition of Wnt/β-catenin signaling. In normal cells, merlin inhibits Src/PDGFR, Rac/PAK/JNK, and maybe N-cadherin ubiquitination as well to keep Y654 unphosphorylated β-catenin staying at AJ together with N-cadherin. In addition, excess cytoplasmic β-catenin can be regulated by proteasome degradation. In merlin-deficient tumor cells, loss of merlin leads to activation of PDGFR and Src (red). β-Catenin is then phosphorylated by Src/PDGFR at Y654 and disassociated with N-cadherin. In further regulation by activated Rac/PAK/JNK (red), β-catenin shuttles into the nucleus to activate transcriptional factors LEF/TCF and then drive the expression of downstream targets, namely, cyclin D1, c-myc, and eventually, proliferation is increased in tumor cells.