Lee Nam-Sihk, Veeranki Sudhakar, Kim Bohye, Kim Leung
Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
Differentiation. 2008 Dec;76(10):1104-10. doi: 10.1111/j.1432-0436.2008.00301.x. Epub 2008 Jul 30.
DB56, the Dictyostelium B56 homolog, displayed high sequence homology to other eukaryotic B56 subunits of the PP2A and a specific association with the PP2A catalytic subunit. Cells lacking DB56, psrA(-), displayed higher PP2A phosphatase activity compared with the wild type, approximately 10 hr of delayed expression of ecmA and ecmB prestalk markers, and inefficient culmination. The prespore marker cotB declined as wild-type cells culminate, but no such decline was observed from psrA(-) cells. Interestingly, psrA(-) cells exhibited higher GSK3 kinase activity. Furthermore, the expression of the dominant negative GSK3 mutant (K84/85M) in psrA(-) cells improved both prestalk and prespore expression patterns similarly to wild-type cells. However, culmination was not restored in psrA(-) cells expressing dominant negative GSK3, which suggests that PP2A/DB56 has an extra target during terminal differentiation. This report shows that PP2A/DB56 controls not only metazoan development, but also non-metazoan cell fate decision processes.
DB56是盘基网柄菌的B56同源物,与PP2A的其他真核生物B56亚基具有高度的序列同源性,并与PP2A催化亚基有特异性结合。缺乏DB56的细胞,即psrA(-)细胞,与野生型相比显示出更高的PP2A磷酸酶活性,前柄标记物ecmA和ecmB的表达延迟约10小时,且细胞聚集效率低下。前孢子标记物cotB在野生型细胞聚集时下降,但在psrA(-)细胞中未观察到这种下降。有趣的是,psrA(-)细胞表现出更高的GSK3激酶活性。此外,在psrA(-)细胞中表达显性负性GSK3突变体(K84/85M),其前柄和前孢子的表达模式与野生型细胞相似,均得到改善。然而,在表达显性负性GSK3的psrA(-)细胞中,细胞聚集并未恢复,这表明PP2A/DB56在终末分化过程中有额外的靶点。本报告表明,PP2A/DB56不仅控制后生动物的发育,还控制非后生动物的细胞命运决定过程。