Cardiff School of Biosciences, Cardiff University, CF10 3AX Cardiff, United Kingdom.
Mol Biol Cell. 2010 Aug 1;21(15):2788-96. doi: 10.1091/mbc.E09-10-0891. Epub 2010 Jun 9.
Glycogen synthase kinase-3 (GSK3) is a highly conserved protein kinase that is involved in several important cell signaling pathways and is associated with a range of medical conditions. Previous studies indicated a major role of the Dictyostelium homologue of GSK3 (gskA) in cell fate determination during morphogenesis of the fruiting body; however, transcriptomic and proteomic studies have suggested that GSK3 regulates gene expression much earlier during Dictyostelium development. To investigate a potential earlier role of GskA, we examined the effects of loss of gskA on cell aggregation. We find that cells lacking gskA exhibit poor chemotaxis toward cAMP and folate. Mutants fail to activate two important regulatory signaling pathways, mediated by phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) and target of rapamycin complex 2 (TORC2), which in combination are required for chemotaxis and cAMP signaling. These results indicate that GskA is required during early stages of Dictyostelium development, in which it is necessary for both chemotaxis and cell signaling.
糖原合酶激酶-3（GSK3）是一种高度保守的蛋白激酶，参与多种重要的细胞信号通路，与多种医学状况有关。先前的研究表明，在果体形态发生过程中，Dictyostelium GSK3 的同源物（gskA）在细胞命运决定中起主要作用；然而，转录组学和蛋白质组学研究表明，GSK3 在 Dictyostelium 发育过程中更早地调节基因表达。为了研究 GskA 潜在的早期作用，我们研究了缺失 gskA 对细胞聚集的影响。我们发现缺失 gskA 的细胞对 cAMP 和叶酸的趋化性较差。突变体无法激活两种重要的调节信号通路，这两种通路分别由磷脂酰肌醇 3,4,5-三磷酸（PIP(3)）和雷帕霉素靶蛋白复合物 2（TORC2）介导，它们共同作用是趋化性和 cAMP 信号所必需的。这些结果表明，GskA 在 Dictyostelium 发育的早期阶段是必需的，它对于趋化性和细胞信号传导都是必需的。
