Nucleo-cytoplasmic shuttling of PAK4 modulates ¦Â-catenin intracellular translocation and signaling

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• 作者：Yan Li ; Yangguang Shao ; Yuxin Tong ; Tao Shen ; Jian Zhang ; Yanshu Li ; Hui Gu ; Feng Li ; ^{fli@mail.cmu.edu.cn} ; ^{lifengphd15@gmail.com}
• 关键词：PAK4 ; Nucleo-cytoplasmic shuttling ; ¦Â-catenin ; Signal transduction
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：1823
• 期：2
• 页码：465-475
• 全文大小：1708 K

文摘

The canonical Wnt/¦Â-catenin signaling pathway plays a central role in development and cancer. The p21-activated kinase 4 (PAK4) involves in a wide range of cellular processes, including cytoskeletal reorganization, cell proliferation, gene transcription and oncogenic transformation. However, the cross talk between the Wnt and PAK4 signaling pathways is poorly understood. Here, we show that PAK4 is a nucleo-cytoplasmic shuttling protein, containing three nuclear export signals (NESs) and two nuclear localization signals (NLSs). PAK4 is exported by the chromosome region maintenance-1 (CRM-1)-dependent pathway and is imported into the nucleus in an importin ¦Á5-dependent manner. PAK4 interacts with and phosphorylates ¦Â-catenin on Ser675, which promotes the TCF/LEF transcriptional activity and stabilizes ¦Â-catenin through inhibition of its degradation. Moreover, nuclear import of PAK4 accompanies with the nuclear import of ¦Â-catenin and increased TCF/LEF transcriptional activity. We further demonstrated that PAK4 associates with the TCF/LEF transcriptional complex by ChIP assays. These findings uncover a novel role for PAK4 in modulating intracellular translocation and signaling of ¦Â-catenin.