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Merlin interacts with LRP6 to block initiation of Wnt/モ-catenin signaling
Soyoung Kim1, Eek-hoon Jho1,*
1Department of Life Science, University of Seoul, Seoul, 130-743, Republic of Korea
Abstract
Merlin, encoded by the NF2 gene, is a tumor suppressor that exerts its function via inhibition of 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 showed that Merlin interacts with LRP6 and inhibits LRP6 phosphorylation, which is a critical step for the initiation of Wnt signaling. We found that treatment of Wnt3a causes phosphorylation of Merlin by PAK1, which leads to the detachment of Merlin from LRP6 and allows the initiation of Wnt/モ-catenin signaling. A higher level of モ-catenin was exhibited in tissues from NF2 patients. Enhanced proliferation and migration caused by knockdown of Merlin in glioblastoma cells were inhibited by the suppression of モ-catenin. Conclusively, these results suggest that sustained Wnt/モ-catenin signaling activity induced by the abrogation of Merlin-mediated inhibition of LRP6 phosphorylation may be a cause of NF2 disease.
Abstract, Accepted Manuscript(in press) [Submitted on June 27, 2016, Accepted on June 27, 2016]
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