title: Merlin, a regulator of Hippo signaling, regulates Wnt/β-catenin signaling.
abstract: Merlin, encoded by the NF2 gene, is a tumor suppressor that exerts its function via inhibiting mitogenic receptors at the plasma membrane. Although multiple mutations in Merlin have been identified in Neurofibromatosis type II (NF2) disease, its molecular mechanism is not fully understood. Here, we show that Merlin interacts with LRP6 and inhibits LRP6 phosphorylation, a critical step for the initiation of Wnt signaling. We found that treatment of Wnt3a caused phosphorylation of Merlin by PAK1, leading to detachment of Merlin from LRP6 and allowing the initiation of Wnt/β-catenin signaling. A higher level of β-catenin was found in tissues from NF2 patients. Enhanced proliferation and migration caused by knockdown of Merlin in glioblastoma cells were inhibited by suppression of β-catenin. Conclusively, these results suggest that sustained Wnt/β-catenin signaling activity induced by abrogation of Merlin-mediated inhibition of LRP6 phosphorylation might be a cause of NF2 disease. [BMB Reports 2016; 49(7): 357-358].
authors.affiliation: Department of Life Science, University of Seoul, Seoul 02504, Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Life Science, University of Seoul, Seoul 02504, Korea.
authors.forename: Eek-Hoon
authors.initials: EH
authors.lastname: Jho
mesh_terms: D045744:Cell Line, Tumor; D020868:Gene Silencing; D000090683:Hippo Signaling Pathway; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000737:chemistry / Q000378:metabolism; D016518:Neurofibromatosis 2 / Q000378:metabolism / Q000473:pathology; D025581:Neurofibromin 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060509:Wnt3A Protein / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D025581:Neurofibromin 2; D060509:Wnt3A Protein; D051176:beta Catenin; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases