Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7
Cell Mol Biol Lett. 2011 Dec;16(4):669-88. doi: 10.2478/s11658-011-0030-z. Epub 2011 Sep 26.
The evolutionarily-conserved protein phosphatase 1 (PP1) plays a central role in dephosphorylation of phosphoproteins during the M phase of the cell cycle. We demonstrate here that the PP1 inhibitor inhibitor-2 protein (Inh-2) induces an M-phase arrest in Xenopus cycling egg extracts. Interestingly, the characteristics of this M-phase arrest are similar to those of mitogen-activated protein kinase (p42MAPK)-induced M-phase arrest. This prompted us to investigate whether Inh-2-induced M-phase arrest was dependent on activation of the p42MAPK pathway. We demonstrate here that MAPK activity is required for Inh-2-induced M-phase arrest, as inhibition of MAPK by PD98059 allowed cycling extracts to exit M phase, despite the presence of Inh-2. We next investigated whether Inh-2 phosphorylation by the MAPK pathway was required to induce an M-phase arrest. We discovered that while p90Rsk (a MAPK protein required for M-phase arrest) is able to phosphorylate Inh-2, this phosphorylation is not required for Inh-2 function. Overall, our results suggest a novel mechanism linking p42MAPK and PP1 pathways during M phase of the cell cycle.
进化保守的蛋白磷酸酶 1（PP1）在细胞周期的 M 相中发挥着去磷酸化磷酸化蛋白的核心作用。我们在此证明，PP1 抑制剂抑制剂-2 蛋白（Inh-2）在爪蟾有丝分裂卵提取物中诱导 M 期阻滞。有趣的是，这种 M 期阻滞的特征与丝裂原激活的蛋白激酶（p42MAPK）诱导的 M 期阻滞相似。这促使我们研究 Inh-2 诱导的 M 期阻滞是否依赖于 p42MAPK 途径的激活。我们在此证明，MAPK 活性是 Inh-2 诱导的 M 期阻滞所必需的，因为 PD98059 抑制 MAPK 允许有丝分裂提取物退出 M 期，尽管存在 Inh-2。我们接下来研究了 MAPK 途径是否需要 Inh-2 磷酸化来诱导 M 期阻滞。我们发现，虽然 p90Rsk（一种需要 M 期阻滞的 MAPK 蛋白）能够磷酸化 Inh-2，但这种磷酸化对于 Inh-2 的功能不是必需的。总的来说，我们的结果表明在细胞周期的 M 相中 p42MAPK 和 PP1 途径之间存在一种新的机制。
