Department of Basic Medical Sciences, University of Lleida. IRBLleida, Lleida, Spain.
Department of Experimental Medicine, University of Lleida. IRBLleida, Lleida, Spain.
J Cell Biochem. 2018 Apr;119(4):3632-3640. doi: 10.1002/jcb.26571. Epub 2018 Jan 5.
β-catenin is a central component of adherent junctions and a key effector of canonical Wnt signaling, in which dephosphorylated Ser/Thr β-catenin regulates gene transcription. β-catenin phosphorylation at Tyr142 (PTyr142 β-catenin), which is induced by receptor and Src family Tyr kinases, represents a previously described β-catenin switch from adhesive to migratory roles. In addition to classical β-catenin roles, phosphorylated Ser/Thr β-catenin and total β-catenin were involved in centrosomal functions, including mitotic spindle formation and centrosome separation. Here we find that PTyr142 β-catenin is present in centrosomes in non-transformed and glioblastoma cells and that, in contrast to the Ser/Thr phosphorylated β-catenin, PTyr142 β-catenin centrosomal levels drop in mitosis. Furthermore, we show that the inhibitor of Spleen Tyrosine Kinase (Syk) piceatannol decreases centrosomal PTyr142 β-catenin levels, indicating that Syk regulates centrosome PTyr142 β-catenin. Our findings suggest that PTyr142 β-catenin and Syk may regulate centrosomal cohesion. This study highlights the contribution of different phosphorylated β-catenin forms to the cell and centrosome cycles.
β-连环蛋白是黏着连接的核心组成部分，也是经典 Wnt 信号通路的关键效应因子，其中去磷酸化的 Ser/Thr 位β-连环蛋白调节基因转录。受体和Src 家族 Tyr 激酶诱导的 Tyr142 位β-连环蛋白磷酸化（PTyr142 β-连环蛋白）代表了β-连环蛋白从黏附到迁移角色的先前描述的转换。除了经典的β-连环蛋白作用外，磷酸化的 Ser/Thr β-连环蛋白和总β-连环蛋白参与中心体功能，包括有丝分裂纺锤体的形成和中心体分离。在这里，我们发现非转化和神经胶质瘤细胞的中心体中存在 PTyr142 β-连环蛋白，与 Ser/Thr 磷酸化的β-连环蛋白相反，PTyr142 β-连环蛋白在有丝分裂期间中心体水平下降。此外，我们表明脾酪氨酸激酶（Syk）抑制剂白藜芦醇可降低中心体的 PTyr142 β-连环蛋白水平，表明 Syk 调节中心体的 PTyr142 β-连环蛋白。我们的发现表明 PTyr142 β-连环蛋白和 Syk 可能调节中心体的黏合。这项研究强调了不同磷酸化β-连环蛋白形式对细胞和中心体周期的贡献。
