YAP（Yes-associated protein）发挥促癌还是抑癌作用存有争议。我们发现YAP定位浆/核内时能分别抑制及促进Dvl磷酸化和入核水平，猜想YAP可能通过影响Dvl磷酸化及定位对Wnt通路发挥双重作用，但具体机制并不清楚。因Dvl的入核序列位于其PDZ结构域与PY基序之间，我们设想磷酸化YAP定位于浆内与PDZ和PY结合封闭了其入核序列，并占据了Dvl与激酶CK1ε生物结合位点PDZ，从而抑制了Dvl的磷酸化及入核。而去磷酸化YAP入核则解除了与Dvl的结合及入核序列抑制,因此增加了Dvl磷酸化及入核。本研究拟构建并转染YAP磷酸化及突变质粒（使其定位于浆/核）、YAP、CK1ε与Dvl结合的剪切体等，通过免疫荧光、IP、GST-pull down及免疫印迹等方法，证实YAP调控Dvl磷酸化及入核作用而影响Wnt通路的分子机制，为防治肺癌的增殖、侵袭提供实验基础。

It is still controversial that YAP（Yes-associated protein）functions as a tumor suppressor or oncoprotein. Our previous study demonstrated that YAP located in cytoplasm could inhibit phosphorylation and nuclear import of Dvl, whereas YAP located in nuclei could upregulate phosphorylation and nuclear import of Dvl. This result indicated that YAP might influence Wnt signaling pathway by regulating phosphorylation and nuclear import of Dvl. However, the mechanism still remains unclear. Given the nuclear localization sequence (NLS) of Dvl was located within the PDZ domain and PY motif, we think that phosphorylated YAP located in cytoplasm could bind to the PDZ domain and PY motif of Dvl, and may block the NLS of Dvl, then influence the nuclear import of Dvl. Furthermore, the binding of YAP with the PDZ domain of Dvl may inhibit the binding of PDZ domain of Dvl with CK1δ/ε, which could inhibit the phosphorylation of Dvl. In contrast, non-phosphorylated YAP located in nuclei could not bind to Dvl, the binding of Dvl with CK1ε was significantly increased, and then the level of phosphorylation of Dvl could be increased. Also, the blocking of NLS of Dvl was depleted, and then the nuclear import of Dvl was increased. To test the hypothesis, we will construct and transfect YAP phosphorylation plasmid and YAP phosphorylated site mutant plasmid (make YAP located in cytoplasm/nuclei), YAP, CK1ε and Dvl plasmids or truncated mutants, and detect the molecular mechanism of YAP influencing Wnt signaling pathway by regulating phosphorylation and nuclear import of Dvl by adopting immunofluorescence, co-Immunoprecipitation, GST-pull down and western blot. These results may provide experimental basis for the prevention and treatment of lung cancer proliferation, invasion and metastasis.