Ossipova Olga, Dhawan Sangeeta, Sokol Sergei, Green Jeremy B A
Department of Cancer Biology, Dana Farber Cancer Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Dev Cell. 2005 Jun;8(6):829-41. doi: 10.1016/j.devcel.2005.04.011.
The kinase PAR-1 plays conserved roles in cell polarity. PAR-1 has also been implicated in axis establishment in C. elegans and Drosophila and in Wnt signaling, but its role in vertebrate development is unclear. Here we report that PAR-1 has two distinct and essential roles in axial development in Xenopus mediated by different PAR-1 isoforms. Depletion of PAR-1A or PAR-1BX causes dorsoanterior deficits, reduced Spemann organizer gene expression, and inhibition of canonical Wnt-beta-catenin signaling. By contrast, PAR-1BY depletion inhibits cell movements and localization of Dishevelled protein to the cell cortex, processes associated with noncanonical Wnt signaling. PAR-1 phosphorylation sites in Dishevelled are required for this translocation, but not for canonical Wnt signaling. We conclude that PAR-1BY is required in the PCP branch and mediates Dsh membrane localization while PAR-1A and PAR-1BX are essential for canonical signaling to beta-catenin, possibly via targets other than Dishevelled.
激酶PAR-1在细胞极性中发挥保守作用。PAR-1也与秀丽隐杆线虫和果蝇的轴建立以及Wnt信号传导有关，但其在脊椎动物发育中的作用尚不清楚。在此我们报告，PAR-1在非洲爪蟾的轴向发育中由不同的PAR-1亚型介导发挥两种不同且必不可少的作用。PAR-1A或PAR-1BX的缺失会导致背前部缺陷、斯佩曼组织者基因表达降低以及经典Wnt-β-连环蛋白信号传导受到抑制。相比之下，PAR-1BY的缺失会抑制细胞运动以及散乱蛋白向细胞皮层的定位，这些过程与非经典Wnt信号传导相关。散乱蛋白中的PAR-1磷酸化位点是这种易位所必需的，但对于经典Wnt信号传导并非必需。我们得出结论，PAR-1BY在平面细胞极性（PCP）分支中是必需的，并介导散乱蛋白的膜定位，而PAR-1A和PAR-1BX对于向β-连环蛋白的经典信号传导至关重要，可能是通过除散乱蛋白之外的其他靶点。
